Table 1.
Family ID | TAA258 | TAA321 | TAA345 | TAA394 | TAA748 | TAA289 | TAA289 | TAA620 | TAA662 | TAA662 | TAA682 | TAA698 | TAA760 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Nucleotide change |
c.813 C>G |
c.6866 G>T |
c.7039_7040 delAT |
c.4467 T>A |
c.7656 C>A |
c.185 G>A |
c.6596 G>A |
c.2093 C>T |
c.8121 C>A |
c.3797 A>T |
c.3428 G>A |
c.4270 C>G |
c.2207 A>G |
Amino acid substitution |
p.C271W | p.C2289F | p.M2347V fs*19 |
p.N1489K | p.C2552* | p.R62H | p.G2199D | p.P698L | p.D2707E | p.Y1266F | p.G1143D | p.P1424A | p.N736S |
Variant type | missense | missense | deletion | missense | nonsense | missense | missense | missense | missense | missense | missense | missense | missense |
Exon | 7 | 55 | 57 | 36 | 61 | 2 | 53 | 16 | 64 | 30 | 27 | 34 | 18 |
Domain | EGF-like #4 |
EGF-like #35 |
TGFBP 7 | EGF-like #26 |
EGF-like #40 |
4-cysteine motif |
EGF-like #33 |
TB3 | - | EGF-like #20 |
EGF-like #13 |
EGF-like #24 |
EGF-like #7 |
phyloPa | 6.519 | 7.8 | ․ | 0.731 | 1.67 | 3.619 | 7.818 | 9.869 | 1.286 | 1.748 | 7.275 | 6.523 | 7.698 |
phastConsb | 1 | 1 | ․ | 0.997 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
GERPc | 4.48 | 5.8 | ․ | 2.15 | 3.84 | 3.26 | 6.07 | 6.06 | 5.38 | 2.28 | 5.6 | 5.81 | 4.79 |
CADDd | 25.3 | 35 | ․ | 24.5 | 49 | 28.8 | 34 | 26.3 | 16.97 | 16.71 | 32 | 23.3 | 24.6 |
FATHMMe | D | D | ․ | D | ․ | D | D | D | T | D | D | D | D |
LRTf | D | D | ․ | D | D | N | D | D | D | N | D | D | D |
Mutation Assessorg |
H | H | ․ | M | ․ | M | N | L | N | N | M | L | M |
Mutation Tasterh |
D | D | ․ | D | A | D | D | D | D | D | D | D | D |
Polyphen2i | D | D | ․ | P | ․ | D | D | D | B | B | D | P | P |
SIFTj | D | D | ․ | D | ․ | D | D | T | T | T | D | D | D |
ExAC All MAFk |
0.0000082 | 0 | 0 | 0 | 0 | 0.0000584 | 0 | 0.0000082 | 0 | 0.0000989 | 0 | 0.0001812 | 0 |
Variant classification |
Pathogenic | Pathogenic | Pathogenic | Pathogenic | Pathogenic | Uncertain significance |
Uncertain significance |
Likely benign |
Uncertain significance |
Uncertain significance |
Uncertain significance |
Uncertain significance |
Likely benign |
PhyloP score: evolutionary conservation score, higher score indicates more conserved site;
PhastCons: evolutionary conservation score ranges from 0 to 1, with 1 being most conserved;
GERP: evolutionary conservation score, higher score indicates more conserved site (17);
CADD: (18);
FATHMM: D=damaging, T=tolerated, (17);
LRT: D=deleterious, N=neutral, (19);
Mutation Assessor: H=functional, high, M=functional, medium, L=non-functional, low, N=non-functional, neutral, (20);
Mutation Taster: A=disease-causing automatic, D=disease-causing, (21);
PolyPhen-2 HVAR: D=probably damaging, P=possibly damaging, B=benign, (22);
SIFT: D=damaging, T=tolerated, (23);
MAF: minor allele frequency in all populations in the Exome Aggregation Consortium (ExAC) database.