85938734 |
Exon 1 (5'UTR) |
Large deletion |
5’UTR-EX1del |
|
Pathogenic |
AVM |
Wooderchak-Donahue (2018) |
 Deletion spans chr5:85,938,734-86,602,815 |
86469478 |
Exon 1 (5'UTR) |
Large deletion |
5’UTR-EX1del |
|
Pathogenic |
CM |
Wooderchak-Donahue (2018) |
 Son (1 month old) died of large brain AVM. Deletion spans chr5:86,469,478-86,613,626. |
86564163 |
Exon 1 (5'UTR) |
Regulatory |
c.-106_-105delinsTT |
|
Suspected benign |
|
Wooderchak-Donahue (2018) |
|
86564476 |
Exon 1 |
Missense |
c.208G>C |
p.Glu70Gln |
VUS |
Suspected HHT |
Wooderchak-Donahue (2018) |
 Lung AVM |
86564477 |
Exon 1 |
Missense |
c.209A>G |
p.Glu70Gly |
Benign |
|
Wooderchak-Donahue (2018) |
|
86564529 |
Exon 1 |
Deletion |
c.261_262del |
p.Gly89Argfs*22 |
Pathogenic |
Suspected HHT |
Wooderchak-Donahue (2018) |
 Epistaxis, telangiectasia, daughter has brain AVM |
86564529 |
Exon 1 |
Deletion |
c.261del |
p.Gly89Glufs*7 |
Pathogenic |
CM, AVM |
Saliou (2017) |
 Spinal AVM with perimedullar subarachnoid hemorrhage |
86564564 |
Exon 1 |
Missense |
c.296C>T |
p.Ala99Val |
Benign |
CM |
Wooderchak-Donahue (2012) ARUP Laboratories |
|
86564614 |
Exon 1 |
Missense |
c.346C>G |
p.Leu116Val |
Pending classification |
|
Maruani (2017) |
 rs149246093 has a frequency of 0.00023 in the European-American population |
86564628 |
Exon 1 |
Silent |
c.360C>A |
p.Pro120Pro |
Suspected benign |
|
Wooderchak-Donahue (2018) |
|
86564633 |
Exon 1 |
Nonsense |
c.365C>A |
p.Ser122* |
Pathogenic |
CM |
Revencu (2013) |
|
86564651 |
Exon 1 |
Deletion |
c.383_384del |
p.Leu128Argfs*29 |
Pathogenic |
CM, AVM |
Saliou (2017) |
 Brain AVM |
86564677 |
Exon 1 |
Duplication |
c.409dup |
p.Leu137Profs*21 |
Pathogenic |
CM, AVM |
Revencu (2013) |
 Right foot AVM |
86564710 |
Exon 1 |
Indel |
c.442_443delinsT |
p.Ala148Trpfs*26 |
Pathogenic |
CM |
Revencu (2013) |
|
86564731 |
Exon 1 |
Nonsense |
c.463G>T |
p.Glu155* |
Pathogenic |
CM |
Revencu (2013) |
|
86564735 |
Exon 1 |
Missense |
c.467G>T |
p.Gly156Val |
VUS |
AVM |
Wooderchak-Donahue (2018) |
 Leg and thigh AVMs |
86564743 |
Exon 1 |
Deletion |
c.475_476del |
p.Leu159fs |
Pathogenic |
CM, AVM, PKWS |
Eerola (2003) ARUP Laboratories |
 4 family members with CM, 1 with CM-AVM, and 1 with PKWS |
86564760 |
Exon 1 |
Nonsense |
c.492C>G |
p.Tyr164* |
Pathogenic |
CM, AVM |
Revencu (2013) |
 Pial AVM, deterioration in speech at 2, mental retardation |
86564780 |
Exon 1 |
Deletion |
c.512del |
p.Ile171fs |
Pathogenic |
CM, AVM |
Eerola (2003) |
 8 family members with CM, 3 with Nuchal CM, 2 with CM-AVM |
86564808 |
Intron 1 |
Splice Site |
c.539+1G>A |
|
Pathogenic |
CM |
Maruani (2017) |
 Bilateral asymmetric CMs across thighs and legs |
86627138 |
Intron 1 |
Intronic |
c.540-27G>A |
|
Benign |
|
Wooderchak-Donahue (2018) |
|
86627165 |
Exon 2-9 |
Large deletion |
EX2-9del |
|
Pathogenic |
CM |
Wooderchak-Donahue (2018) |
|
86627181 |
Exon 2 |
Deletion |
c.556_562del |
p.Leu186Glufs*3 |
Pathogenic |
CM, AVF |
Saliou (2017) |
 Multiple brain AVFs, mucocutaneous telangiectasia, hepato- and splenomegaly |
86627236 |
Exon 2 |
Duplication |
c.611dup |
p.Tyr204* |
Pathogenic |
CM |
Wooderchak-Donahue (2018) |
|
86627238 |
Exon 2 |
Deletion |
c.613_617del |
p.Leu205fs |
Pathogenic |
CM |
Revencu (2008) ARUP Laboratories |
 Optic glioma (before 12y), lipoma (before 10y) |
86627281 |
Exon 2 |
Nonsense |
c.656C>G |
p.Ser219* |
Pathogenic |
CM |
Revencu (2008) |
|
86628365 |
Exon 3 |
Indel |
c.734_737delinsAAA |
p.Arg245fs |
Pathogenic |
CM |
Wijn (2012) |
|
86628437 |
Exon 3 |
Deletion |
c.806_810del |
p.Leu269fs |
Pathogenic |
CM, PKWS |
Revencu (2008) |
 Cardiac overload |
86628462 |
Intron 3 |
Splice Site |
c.828+3A>T |
|
Pathogenic |
CM, AVM/AVF |
Revencu (2008) ARUP Laboratories |
|
86628462 |
Intron 3 |
Splice Site |
c.828+3A>T |
|
Pathogenic |
CM |
Wooderchak-Donahue (2018) |
 Right thigh epidermal nevus |
86629072 |
Intron 3 |
Intronic |
c.829-12del |
|
Benign |
|
ARUP Laboratories |
|
86629075 |
Intron 3 |
Splice Site |
c.829-9G>A |
|
Pending classification |
CM |
Hershkovitz (2008) |
 4 month old with red maulae on cheek, ear, and leg. Small arteriovenous shunt in outer ear. Identical twin brother has 2 similar lesions on arm. |
86629083 |
Intron 3 |
Splice Site |
c.829-1G>A |
|
Pathogenic |
CM, AVM |
Revencu (2013) |
 Left arm AVM |
86629108 |
Exon 4 |
Nonsense |
c.853C>T |
p.Arg285* |
Pathogenic |
CM |
Hershkovitz (2008) ARUP Laboratories |
 6 y old with epilepsy and red maculae on his cheek, ear, shoulder, and arm. Similar lesions in other family members who denied any neurological complaint. Originally reported as p.Gln285X |
86629155 |
Intron 4 |
Splice Site |
c.899+1G>T |
|
Pathogenic |
CM, AVM |
Revencu (2013) |
 Ear AVM |
86633842 |
Exon 5 |
Duplication |
c.951dupG |
p.Met318fs |
Pathogenic |
CM |
Revencu (2008) |
|
86633848 |
Exon 5 |
Nonsense |
c.957G>A |
p.Trp319* |
Pathogenic |
CM, PKWS |
Revencu (2008) |
 Cardiac overload |
86564163 |
Exon 5 |
Deletion |
c.934_938del |
p.Glu312Argfs*14 |
Pathogenic |
CM, PKWS |
Flores Daboub (2020) |
 Somatic (3.6%), Likely de novo |
86633909 |
Intron 5 |
Splice Site |
c.1017+1G>T |
|
Pathogenic |
CM, PKWS |
Revencu (2008) |
 Cardiac overload |
86633973 |
Intron 5 |
Intronic |
c.1017+65G>A |
|
Benign |
|
ARUP Laboratories |
 Polymorphism in normal and affected individuals. |
86642502 |
Exon 7 |
Nonsense |
c.1063A>T |
p.Lys355* |
Pathogenic |
CM, AVM |
Lapinski (2018) |
|
86642543 |
Intron 7 |
Splice Site |
c.1102+2T>C |
|
Pathogenic |
CM, AVM |
Saliou (2017) |
 Brain AVM |
86642551 |
Intron 7 |
Intronic |
c.1102+10T>C |
|
Suspected benign |
|
Wooderchak-Donahue (2018) |
|
86645029 |
Intron 7 |
Splice Site |
c.1103-2A>G |
|
Pathogenic |
CM, T |
Wooderchak-Donahue (2018) |
 Shortness of breath |
86645120 |
Exon 8 |
Nonsense |
c.1192C>T |
p.Arg398* |
Pathogenic |
CM, AVM/AVF |
Revencu (2008) |
 Epilepsy, hydrocephaly |
86645136 |
Exon 8 |
Duplication |
c.1208dupC |
p.Thr404fs |
Pathogenic |
CM, AVM/AVF |
Revencu (2008) |
|
86645148 |
Exon 8 |
Deletion |
c.1220_1223del |
p.Asn407Serfs*3 |
Pathogenic |
CM |
Revencu (2013) Wooderchak-Donahue (2018) |
 Birthmarks |
86645176 |
Exon 8 |
Nonsense |
c.1248T>G |
p.Tyr416* |
Pathogenic |
CM |
Macmurdo (2016) |
 Lymphedema, chylothorax, and overgrowth were also noted in the newborn. Her mother also had CMs in which a somatic second hit (RASA1 c.2245C>T, p.Arg749*) was discovered in the CM lesion. |
86648989 |
Exon 9 |
Insertion |
c.1268_1269dup |
p.Asp424* |
Pathogenic |
CM, AVM |
Lapinski (2018) |
 Reported as c.1269_1270insTA, p.Ile423* (Lapinski, 2018) |
86648997 |
Exon 9 |
Missense |
c.1277A>G |
p.Tyr426Cys |
Pending classification |
CM |
Revencu (2008) |
 Typical solitary CM |
86648999 |
Exon 9 |
Nonsense |
c.1279C>T |
p.Arg427* |
Pathogenic |
CM, AVM/AVF |
Revencu (2008) ARUP Laboratories |
 CM-AVM |
86649010 |
Exon 9 |
Deletion |
c.1290_1291del |
p.Gln430Hisfs*3 |
Pathogenic |
CM, PKWS |
Revencu (2013) |
 Left leg hypertrophy |
86649030 |
Exon 9 |
Missense |
c.1310T>G |
p.Leu437Arg |
VUS |
CM |
Wooderchak-Donahue (2012) ARUP Laboratories |
|
86649057 |
Intron 9 |
Splice Site |
c.1332+5G>A |
|
Pending classification |
CM |
Revencu (2008) |
|
86649058 |
Intron 9 |
Splice Site |
c.1332+6T>G |
|
VUS |
|
Wooderchak-Donahue (2018) |
 Suspected PTEN hamartoma tumor syndrome; overgrowth; facial venous malformation |
86658371 |
Exon 10 |
Nonsense |
c.1336C>T |
p.Gln446* |
Pathogenic |
CM, PKWS, AVM |
Eerola (2003) Revencu (2008) |
 7 family members with CM, 1 with Nuchal CM, 2 with CM-AVM |
86658377 |
Exon 10 |
Nonsense |
c.1342C>T |
p.Gln448* |
Pathogenic |
CM, AVM |
Revencu (2013) |
 Tongue AVM |
86658378 |
Exon 10 |
Indel |
c.1343_1346delinsCATG |
p.Gln448fs |
Pathogenic |
CM |
Hershkovitz (2008b) |
 2 day old infant with limb enlargement and cutaneous vascular malformations on leg and neck. Patient's sister had a facial AVM. Four other siblings and the patient's mother displayed CMs. |
86658385 |
Exon 10 |
Insertion |
c.1350_1351insT |
p.Asn451* |
Pathogenic |
CM, PKWS |
Revencu (2008) |
|
86658387 |
Exon 10 |
Missense |
c.1352A>G |
p.Asn451Ser |
Pending classification |
|
Maruani (2017) |
 rs529871259 has a frequency of 0.002 in the African population |
86658397 |
Exon 10 |
Insertion |
c.1362_1363insTCAGT |
p.Asp455fs |
Pathogenic |
CM |
Revencu (2008) |
|
86658419 |
Exon 10 |
Deletion |
c.1384_1388del |
p.Thr462Profs*3 |
Pathogenic |
CM |
Revencu (2013) |
|
86658421 |
Exon 10 |
Insertion |
c.1386_1387insCT |
p.Ile463fs |
Pathogenic |
CM, AVM |
Thiex (2010) |
|
86658437 |
Exon 10 |
Deletion |
c.1402_1403del |
p.Lys468fs |
Pathogenic |
CM, AVM |
Wooderchak-Donahue (2012) ARUP Laboratories |
 Reported as c.1401_1402delAA |
86658475 |
Exon 10 |
Nonsense |
c.1440T>G |
p.Tyr480* |
Pathogenic |
CM |
Revencu (2013) |
|
86658489 |
Intron 10 |
Splice Site |
c.1453+1del |
|
Pathogenic |
CM, AVF |
Thiex (2010) |
|
86659158 |
Intron 10 |
Intronic |
c.1454-7delT |
|
Benign |
|
Wooderchak-Donahue (2018) |
|
86659166 |
Exon 11 |
Deletion |
c.1455del |
p.Gly487Glufs*11 |
Pathogenic |
CM, AVM |
Saliou (2017) |
 Brain AVM |
86659191 |
Exon 11 |
Duplication |
c.1480dup |
p.Tyr494fs |
Pathogenic |
CM, PKWS |
Revencu (2008) |
|
86659201 |
Exon 11 |
Nonsense |
c.1490T>G |
p.Leu497* |
Pathogenic |
CM, AVM/AVF |
Revencu (2008) |
|
86659204 |
Exon 11 |
Deletion |
c.1493_1494del |
p.Glu498fs |
Pathogenic |
CM |
Wooderchak-Donahue (2012) ARUP Laboratories |
 Reported as c.1491_1492delAG |
86659205 |
Exon 11 |
Duplication |
c.1495_1496dup |
p.Ser500Valfs*21 |
Pathogenic |
CM |
Revencu (2013) |
 Reported as c.1494_1495dup, p.Gly499Argfs*22 |
86659218 |
Exon 11 |
Nonsense |
c.1507C>T |
p.Gln503* |
Pathogenic |
CM, AVM |
Boyden (2012) |
|
86659220 |
Exon 11 |
Deletion |
c.1509del |
p.Gln503Hisfs*17 |
Pathogenic |
CM, AVM |
Saliou (2017) |
 Brain AVM |
86659224 |
Exon 11 |
Insertion |
c.1513_1514insAA |
p.Ile505Lysfs*16 |
Pathogenic |
CM, AVM |
Wooderchak-Donahue (2018) |
 Bilateral brain AVM, left arm hypertrophy, telangiectasia |
86659228 |
Exon 11 |
Insertion |
c.1517_1518dup |
p.Phe507Ilefs*14 |
Pathogenic |
CM |
Wooderchak-Donahue (2018) |
 """Checkerboard"" pattern of vascular malformations" |
86659228 |
Exon 11 |
Deletion |
c.1517_1520del |
p.Tyr506Leufs*13 |
Pathogenic |
CM, PKWS |
Revencu (2013) |
 Left leg hypertrophy |
86659245 |
Exon 11 |
Nonsense |
c.1534C>T |
p.Arg512* |
Pathogenic |
CM, AVM |
Revencu (2013) Wooderchak-Donahue (2018) |
 Hypertrophy of limb, portwine stain. Also identified as a RASA1 somatic second hit in a CM lesion in a patient with a germline RASA1 c.2125C>T, p.Arg709* mutation (Lapinski 2018) |
86659278 |
Exon 11 |
Deletion |
c.1567_1568del |
p.Ser523Cysfs*9 |
Pathogenic |
AVF |
Saliou (2017) |
 Multiple brain AVFs |
86659283 |
Exon 11 |
Duplication |
c.1572_1575dup |
p.Ser526fs |
Pathogenic |
CM, PKWS |
Revencu (2008) |
 Cardiac overload, tetralogy of Fallot, superficial basal cell carcinoma (33y) |
86659290 |
Exon 11 |
Deletion |
c.1579_1582delGTCT |
p.Val527fs |
Pathogenic |
CM, AVM |
Eerola (2003) ARUP Laboratories |
 5 family members with CM, 1 with Nuchal CM, 1 with CM-AVM |
86659294 |
Exon 11 |
Missense |
c.1583A>G |
p.Tyr528Cys |
Benign |
|
Wooderchak-Donahue (2018) |
 Variant was originally classified as a VUS because it had been reported in individuals with CMs (Revencu 2013). Hernandez 2015 also identified this variant in a case suspected to have HHT. It was later found to be present in ~1% of Southeast Asians (ExAC database) and was reclassified to benign. |
86659300 |
Exon 11 |
Missense |
c.1589T>A |
p.Val530Asp |
Pending classification |
CM, AVM |
Revencu (2013) |
 Brainstem AVM (brain haemorrhage with facial palsy at 3 weeks); Left leg AVM; Basal cell carcinoma in two individuals |
86659305 |
Exon 11 |
Duplication |
c.1594dup |
p.Asp532Glyfs*2 |
Pathogenic |
AVM |
Saliou (2017) |
 Brain AVM |
86659307 |
Exon 11 |
Deletion |
c.1596 1597del |
p.Asp532Glufs*17 |
Pathogenic |
CM, AVM |
Revencu (2013) |
 Right hand AVM |
86665625 |
Intron 11 |
Splice Site |
c.1611-7delT |
|
Benign |
|
ARUP Laboratories |
|
86665636 |
Exon 12 |
Duplication |
c.1616dup |
p.Asn539fs |
Pathogenic |
CM |
Wooderchak-Donahue (2012) ARUP Laboratories |
 Reported as c.1617dupA |
86665638 |
Exon 12 |
Missense |
c.1619G>A |
p.Cys540Tyr |
Pending classification |
CM, AVF |
Eerola (2003) |
 4 family members with CM, 2 with Nuchal CM, 1 with CM-AVF |
86665655 |
Exon 12 |
Nonsense |
c.1636C>T |
p.Gln546* |
Pathogenic |
CM, AVM/AVF |
Revencu (2008) |
|
86665668 |
Exon 12 |
Missense |
c.1649A>T |
p.Glu550Val |
VUS |
CM |
Wooderchak-Donahue (2018) |
|
86665685 |
Exon 12 |
Splice Site |
c.1666_1698+15del |
|
Pathogenic |
CM, AVM |
Thiex (2010) |
|
86665702 |
Exon 12 |
Duplication |
c.1682_1683dup |
p.Pro562fs |
Pathogenic |
CM, AVM/AVF |
Revencu (2008) |
 Cardiac failure, epilepsy, hemorrhages, arterial septal defect II/patent foramen ovale |
86665718 |
Intron 12 |
Splice Site |
c.1698+1G>T |
|
Pathogenic |
CM |
Revencu (2013) |
|
86665719 |
Intron 12 |
Splice Site |
c.1698+2dup |
|
Pathogenic |
CM, AVM |
Wooderchak-Donahue (2018) Overcash (2015) |
 Several hemangiomas |
86665720 |
Intron 12 |
Splice Site |
c.1698+3_1698+4insT |
|
Pending classification |
CM, PKWS |
Revencu (2008) |
 Pulmonary stenosis |
86667939 |
Exon 13 |
Nonsense |
c.1703G>A |
p.Trp568* |
Pathogenic |
CM, AVM |
Lapinski (2018) |
|
86667953 |
Exon 13 |
Nonsense |
c.1717C>T |
p.Gln573* |
Pathogenic |
CM, AVM |
Thiex (2010) |
|
86667962 |
Exon 13 |
Duplication |
c.1726dup |
p.Cys576Leufs*7 |
Pathogenic |
CM, AVM |
Revencu (2013) |
 Left arm AVM |
86668007 |
Exon 13 |
Duplication |
c.1771dup |
p.Arg591fs |
Pathogenic |
CM |
Wooderchak-Donahue (2012) ARUP Laboratories |
 Reported as c.1771_2insC |
86669867 |
Intron 13 |
Intronic |
c.1777-113G>A |
|
Benign |
|
Wooderchak-Donahue (2018) |
|
86670037 |
Exon 14 |
Missense |
c.1834A>G |
p.Thr612Ala |
VUS |
Suspected HHT |
Wooderchak-Donahue (2018) |
 Brain AVM |
86670073 |
Exon 14 |
Nonsense |
c.1870C>T |
p.Gln624* |
Pathogenic |
CM, AVM/AVF |
Revencu (2008) ARUP Laboratories |
|
86670080 |
Exon 14 |
Missense |
c.1877C>A |
p.Ala626Glu |
Pending classification |
CM |
Revencu (2013) |
|
86670706 |
Exon 15 |
Deletion |
c.1984_1988del |
p.Thr662Glufs*6 |
Pathogenic |
CM |
Wooderchak-Donahue (2018) |
 Left thigh hypertrophy |
86670711 |
Exon 15 |
Deletion |
c.1989 1992del |
p.Lys664Alafs*13 |
Pathogenic |
CM, AVM |
Revencu (2013) |
 Left arm AVM |
86670734 |
Intron 15 |
Splice Site |
c.2011+1G>C |
|
Pathogenic |
CM |
Wooderchak-Donahue (2018) |
|
86670789 |
Intron 15 |
Intronic |
c.2011+56A>G |
|
Benign |
|
Wooderchak-Donahue (2018) |
|
86672210 |
Exon 16-20 |
Large deletion |
EX16-20del |
|
Pathogenic |
CM |
Wooderchak-Donahue (2018) |
|
86672224 |
Exon 16 |
Nonsense |
c.2026C>T |
p.Gln676* |
Pathogenic |
CM |
Revencu (2008) ARUP Laboratories |
|
86672233 |
Exon 16 |
Nonsense |
c.2035C>T |
p.Arg679* |
Pathogenic |
CM, AVM, PKWS |
Revencu (2013) Wooderchak-Donahue (2018) |
 Right leg hypertrophy; another proband has CM, a cutaneous AVM, and telangiectasia |
86672264 |
Exon 16 |
Nonsense |
c.2066G>A |
p.Trp689* |
Pathogenic |
CM |
Wooderchak-Donahue (2018) |
 Telangiectasia was also reported |
86672282 |
Exon 16 |
Missense |
c.2084A>T |
p.His695Leu |
VUS |
CM, AVM/AVF |
Wooderchak-Donahue (2012) ARUP Laboratories |
|
86672317 |
Exon 16 |
Missense |
c.2119C>T |
p.Arg707Cys |
Pending classification |
CM, AVM |
Kwong (2015) |
 Vein of Galen malformation identified during sonography of a pregnant mother during the third trimester. The malformation was later assessed by MRI and MR angiography. |
86672323 |
Exon 16 |
Nonsense |
c.2125C>T |
p.Arg709* |
Pathogenic |
CM, AVM/AVF, PKWS |
Revencu (2008) |
 Vericose veins, Cardiac failure |
86672329 |
Exon 16 |
Nonsense |
c.2131C>T |
p.Arg711* |
Pathogenic |
CM, AVF |
Revencu (2013) Wooderchak-Donahue (2018) |
 Hypertrophy of face |
86672353 |
Exon 16 |
Indel |
c.2155_2156delinsTA |
p.Pro719* |
Pathogenic |
|
Wooderchak-Donahue (2018) |
 Clinical information not reported |
86672383 |
Intron 16 |
Splice Site |
c.2184+1del |
|
Pathogenic |
CM, PKWS |
Revencu (2008) |
 Patent ductus arteriosus, arterial septal defect, pulmonary stenosis, prolapsed tricuspid valve |
86672696 |
Intron 16 |
Splice Site |
c.2185-2A>C |
|
Pathogenic |
CM |
Wooderchak-Donahue (2018) |
 Cyst-like lesion on cheek, congenital ptosis |
86672697 |
Intron 16 |
Splice Site |
c.2185-1G>A |
|
Pathogenic |
CM |
Revencu (2008) |
|
86672722 |
Exon 17 |
Missense |
c.2209G>A |
p.Val737Ile |
VUS |
CM |
Wooderchak-Donahue (2018) |
 Telangiectasia was also reported |
86672738 |
Exon 17 |
Nonsense |
c.2225C>A |
p.Ser742* |
Pathogenic |
CM, AVM |
Wooderchak-Donahue (2012) ARUP Laboratories |
 Facial hemangioma, macrocephaly, seizures |
86672752 |
Exon 17 |
Nonsense |
c.2239C>T |
p.Gln747* |
Pathogenic |
CM, AVM |
Wooderchak-Donahue (2012) ARUP Laboratories |
|
86672758 |
Exon 17 |
Nonsense |
c.2245C>T |
p.Arg749* |
Pathogenic |
CM |
Revencu (2013) Wooderchak-Donahue (2018) |
 Facial portwine stain. Somatic second hit identified in CM lesion (Macmurdo 2016). |
86672765 |
Exon 17 |
Duplication |
c.2252_2255dup |
p.Ala753fs |
Pathogenic |
CM |
Hershkovitz (2008) |
 15 y old with congenital hypophyseal insufficiency and multiple red maculae on cheek, oral mucosa, and arm. His mother, aunt, and cousin, who suffered from congenital hand deformity, displayed similar vascular malformations. Originally reported as c.2252_2255dupTCAT het frameshift |
86672782 |
Exon 17 |
Nonsense |
c.2269del |
p.Leu757* |
Pathogenic |
AVM/AVF, PKWS |
Wooderchak-Donahue (2018) |
 Leg lymphangioma, tetralogy of fallot, cellulitis. This case also had a PTEN c.1026+1G>A mutation. |
86672801 |
Exon 17 |
Missense |
c.2288A>T |
p.Glu763Val |
Pending classification |
CM, AVM/AVF |
Revencu (2008) |
 Vein of Galen aneurysmal malformation, cardiac failure, epilepsy, died rapidly after birth |
86672820 |
Exon 17 |
Silent |
c.2307G>A |
p.Leu769Leu |
Suspected benign |
|
Wooderchak-Donahue (2018) |
|
86672823 |
Exon 17 |
Duplication |
c.2310dup |
p.Cys771Metfs*5 |
Pathogenic |
CM |
Wooderchak-Donahue (2018) |
|
86672842 |
Exon 17 |
Nonsense |
c.2329G>T |
p.Glu777* |
Pathogenic |
CM, AVF |
Thiex (2010) |
|
86672849 |
Exon 17 |
Deletion |
c.2336_2337del |
p.Ser779fs |
Pathogenic |
CM, AVM |
Eerola (2003) |
 3 family members with CM, 1 with Nuchal CM, 2 with CM-AVM |
86672854 |
Exon 17 |
Nonsense |
c.2341G>T |
p.Glu781* |
Pathogenic |
CM, AVM/AVF |
Revencu (2008) |
 Hydrocephaly |
86672858 |
Intron 17 |
Splice Site |
c.2344+1G>A |
|
Pathogenic |
CM |
Wooderchak-Donahue (2018) |
|
86672858 |
Intron 17 |
Splice Site |
c.2344+1G>C |
|
Pathogenic |
CM, AVM |
Revencu (2013) |
 Facial AVM |
86674233 |
Exon 18 |
Nonsense |
c.2365C>T |
p.Arg789* |
Pathogenic |
CM, AVM/AVF |
Revencu (2008) ARUP Laboratories |
 Angiolipoma (1y) |
86674290 |
Exon 18 |
Nonsense |
c.2422C>T |
p.Gln808* |
Pathogenic |
CM, PKWS |
Revencu (2008) |
|
86674309 |
Exon 18 |
Nonsense |
c.2441del |
p.Leu814* |
Pathogenic |
CM, AVM |
Palmyre (2017) Saliou (2017) |
|
86674318 |
Exon 18 |
Deletion |
c.2450_2451del |
p.Ser817fs |
Pathogenic |
CM, AVM/AVF |
Revencu (2008) |
|
86674319 |
Exon 18 |
Duplication |
c.2451dup |
p.Ile818Tyrfs*12 |
Pathogenic |
CM |
Wooderchak-Donahue (2018) |
|
86674325 |
Exon 18 |
Indel |
c.2457_2460delinsT |
p.Leu819_Lys820delinsPhe |
Pathogenic |
CM, AVM |
Revencu (2013) |
 Facial AVM; Right hand AVM |
86674335 |
Exon 18 |
Duplication |
c.2467dup |
p.Glu823Glyfs*7 |
Pathogenic |
CM |
Whitaker (2016) |
 20 CMs on the limbs and neck |
86675450 |
Intron 18 |
Intronic |
c.2488-102G>A |
|
Benign |
|
ARUP Laboratories |
|
86675511 |
Intron 18 |
Intronic |
c.2488-41A>C |
|
Benign |
|
ARUP Laboratories |
|
86675550 |
Intron 18 |
Splice Site |
c.2488-2A>G |
|
Pathogenic |
CM |
Revencu (2008) |
|
86675551 |
Intron 18 |
Splice Site |
c.2488-1_2490del |
|
Pathogenic |
CM, AVM/AVF |
Revencu (2008) |
 Non-small-cell lung cancer (32y), hemoptysis. Reported as c.2488-1delGTTA. |
86675564 |
Exon 19 |
Deletion |
c.2500_2501del |
p.Lys834Valfs*5 |
Pathogenic |
CM |
Revencu (2013) |
|
86675577 |
Exon 19 |
Duplication |
c.2513dup |
p.Asn838Lysfs*2 |
Pathogenic |
AVM |
Saliou (2017) |
 Brain AVM |
86675578 |
Exon 19 |
Insertion |
c.2514_2515insA |
p.Glu839fs |
Pathogenic |
CM |
Revencu (2008) |
|
86675596 |
Exon 19 |
Deletion |
c.2532_2536del |
p.Leu845fs |
Pathogenic |
CM, AVM/AVF |
Revencu (2008) |
 De novo mutation in monozygotic twins. Vein of Galen aneurysmal malformation and cardiac failure in one. Typical solitary CM in two family members. |
86675643 |
Exon 19 |
Deletion |
c.2579_2582del |
p.Phe860fs |
Pathogenic |
CM, AVM/AVF |
Revencu (2008) |
 Ectopic thyroid and parathyroid |
86675662 |
Exon 19 |
Duplication |
c.2598dup |
p.Pro867Serfs*18 |
Pathogenic |
CM |
Wooderchak-Donahue (2018) |
|
86675668 |
Intron 19 |
Splice Site |
c.2603+1G>A |
|
Pathogenic |
CM, AVM |
Revencu (2008) ARUP Laboratories |
 Chylous ascites |
86675669 |
Intron 19 |
Splice Site |
c.2603+2dup |
|
Pathogenic |
CM |
Revencu (2008) ARUP Laboratories |
 Ureteral reflux, epispadias. Reported as c.2603+2_2603+3insT |
86675671 |
Intron 19 |
Splice Site |
c.2603+4dup |
|
Pending classification |
CM |
Revencu (2008) |
 Reported as c.2603+4_2603+5insA |
86675671 |
Intron 19 |
Splice Site |
c.2603+4del |
|
Pathogenic |
CM, AVM |
Wooderchak-Donahue (2018) |
 Case was originally suspected to have HHT due to telangiectasia and a brain AVM, but HHT molecular testing was negative |
86675672 |
Intron 19 |
Splice Site |
c.2603+5G>T |
|
Pending classification |
CM, PKWS |
Revencu (2008) |
 Neurofibromas (53y) |
86675672 |
Intron 19 |
Splice Site |
c.2603+5G>C |
|
Pathogenic |
CM |
Buhl (2012) |
|
86675852 |
Intron 19 |
Intronic |
c.2603+185T>C |
|
Benign |
|
Wooderchak-Donahue (2018) |
|
86676204 |
Intron 19 |
Intronic |
c.2604-122T>C |
|
Benign |
|
ARUP Laboratories |
|
86676324 |
Intron 19 |
Splice Site |
c.2604-2A>C |
|
Pathogenic |
CM |
Wooderchak-Donahue (2018) |
 Hypertrophy of lower extremity |
86676325 |
Intron 19 |
Splice Site |
c.2604-1_2605del |
|
Pathogenic |
CM |
Wooderchak-Donahue (2018) |
|
86676326 |
Exon 20 |
Splice Site |
c.2604G>T |
p.Pro868Pro |
Pathogenic |
CM, AVM/AVF |
Wooderchak-Donahue (2018) |
 Mutation was shown to disrupt splicing by mRNA sequencing. Patient's brain AVM/AVF was identified through prenatal ultrasound and confirmed by MRI. |
86676330 |
Exon 20 |
Silent |
c.2608T>C |
p.Leu870Leu |
Benign |
|
Wooderchak-Donahue (2018) |
|
86676354 |
Exon 20 |
Nonsense |
c.2632C>T |
p.Gln878* |
Pathogenic |
CM, PKWS |
Revencu (2013) |
 Right leg hypertrophy (and ulceration); hydrops fetalis |
86679516 |
Intron 20 |
Intronic |
c.2691-14del |
|
Benign |
|
ARUP Laboratories |
 Originially reported as c.2691-16delA |
86679519 |
Intron 20 |
Intronic |
c.2691-11C>T |
|
Suspected benign |
|
Wooderchak-Donahue (2018) |
|
86679530 |
Exon 21-25 |
Large deletion |
EX21-25del |
|
Pathogenic |
AVM |
Wooderchak-Donahue (2018) |
 Facial AVM |
86679537 |
Exon 21 |
Deletion |
c.2698_2701del |
p.Val900Phefs*10 |
Pathogenic |
CM, AVF |
Wooderchak-Donahue (2018) |
|
86679542 |
Exon 21 |
Deletion |
c.2703del |
p.Leu902Phefs*9 |
Pathogenic |
CM, AVM |
Saliou (2017) |
 Brain AVM |
86679546 |
Exon 21 |
Nonsense |
c.2707C>T |
p.Arg903* |
Pathogenic |
CM, AVM |
Revencu (2013) Wooderchak-Donahue (2018) |
|
86682617 |
Intron 22 |
Intronic |
c.2848-26T>C |
|
Benign |
|
Wooderchak-Donahue (2018) |
|
86564163 |
Exon 23 |
Deletion |
c.2925del |
p.Asn976Metfs*20 |
Pathogenic |
CM, PKWS |
Flores Daboub (2020) |
 Somatic (4.2%), Likely de novo |
86682721 |
Intron 23 |
Splice Site |
c.2925+1G>T |
|
Pathogenic |
|
Wooderchak-Donahue (2018) |
 "3 month old with ""large right periocular lesion""" |
86682721 |
Intron 23 |
Splice Site |
c.2925+1del |
|
Pathogenic |
CM |
Wooderchak-Donahue (2018) |
|
86682725 |
Intron 23 |
Splice Site |
c.2925+5G>C |
|
Pathogenic |
CM, AVM |
Revencu (2013) |
 Spinal AVM with left leg paralysis at 2 years old |
86685211 |
Exon 24 |
Deletion |
c.2927del |
p.Asn976Metfs*20 |
Pathogenic |
CM |
Durrington (2013) |
 Macular telangiectasia affecting the face, neck, chest, and abdomen. Presented during pregnancy. |
86685261 |
Exon 24 |
Deletion |
c.2977del |
p.Arg993Valfs*3 |
Pathogenic |
CM, AVM, PKWS |
Revencu (2013) |
 Vein of Galen aneurysmal malformation (stroke), left arm hypertrophy |
86685308 |
Exon 24 |
Deletion |
c.3024del |
p.Glu1008Aspfs*16 |
Pathogenic |
CM, AVM |
Revencu (2013) |
 Vein of Galen aneurysmal malformation (stroke at 3 years old), developmental delay |
86685312 |
Exon 24 |
Nonsense |
c.3028C>T |
p.Arg1010* |
Pathogenic |
CM, AVM |
Revencu (2008) Wooderchak-Donahue (2018) |
 Vestibular Schwannoma (26y); 13 year old male with suspected HHT with a lung AVM and telangiectasia |
86685322 |
Exon 24 |
Deletion |
c.3038_3054del |
p.Ser1013Thrfs*27 |
Pathogenic |
CM |
Revencu (2013) |
|
86685327 |
Exon 24 |
Nonsense |
c.3043G>T |
p.Glu1015* |
Pathogenic |
Suspected HHT |
Hernandez (2015) |
|
86685336 |
Exon 24 |
Deletion |
c.3052delG |
p.Ala1018fs |
Pathogenic |
CM |
Revencu (2008) |
|
86685339 |
Exon 24 |
Nonsense |
c.3055C>T |
p.Gln1019* |
Pathogenic |
CM |
Revencu (2013) |
|
86685345 |
Intron 24 |
Splice Site |
c.3060+1dup |
|
Pathogenic |
Suspected HHT |
Wooderchak-Donahue (2018) |
 Telangiectasia was also reported |
86685365 |
Intron 24 |
Intronic |
c.3060+21A>G |
|
Benign |
CM |
Wooderchak-Donahue (2012) ARUP Laboratories |
|
86686623 |
Exon 25 |
Silent |
c.3067T>C |
p.Leu1023Leu |
Pending classification |
|
Haga (2002) |
 SNP rs3747704 discovered during the Japanese Millennium Genome Project. |
86686665 |
Exon 25 |
Deletion |
c.3109_3112del |
p.Gln1037Thrfs*63 |
Pathogenic |
CM, AVM |
Revencu (2013) |
 Left leg AVM; Naevus anemicus |
86686797 |
3'UTR |
Regulatory |
c.*97A>G |
|
Benign |
CM |
Wooderchak-Donahue (2012) ARUP Laboratories |
 Reported as c.3144+97A>G |