Table 2.

COL5A1 single nucleotide variants with predicted deleterious effect by in silico analysis identified among individuals enrolled in the mFMD cohort study. All variants are located on chromosome 9, cytoband 9q34.3. Position denotes genomic location on reference genome GRCh37.

Reference SNP ClusterID	rs147589613	rs142114921	rs772379819	rs878853652	rs147329970	rs368305377	rs765217611
Genome Location
Position	137591818	137591844	137623481	137642433	137648614	137702117	137709645
COL5A1 Exon	3	3	8	12	17	44	54
Variant Effect
Base Change	c.C341A	c.C367G	c.C1304T	c.G1540A	c.C1831T	c.C3491T	c.C4198T
Amino Acid Change	p.(Ala114Asp)	p.(Gln123Glu)	p.(Pro435Ala)	p.(Gly514Ser)	p.(Arg611Trp)	p.(Pro1164Leu)	p.(Pro1400Ser)
Population Allele Frequency
gnomAD	0.0005773	0.0002093	3.65E–05	NR	7.31E–05	0.0001082	1.11E–05
ExAC	0.0006122	0.0001655	0.0000498	NR	0.00009902	0.0001323	0.00001147
Locus Location
Residue Modification	None	None	None	None	None	None	None
Domain	N-pro	N-pro	N-pro	Helix	Helix	Helix	Helix
Pathogenicity Estimation
Ensemble Score Prediction
MetaSVM	D	T	D	D	D	D	D
MetaLR	D	T	D	D	D	D	D
M.CAP	D	T	D	D	D	D	D
Functional Prediction
SIFT	D	T	D	D	D	D	T
Polyphen2 HDIV	P	D	D	D	D	D	D
Polyphen2 HVAR	P	D	D	D	D	P	D
LRT pred	U	U	U	U	U	U	U
MutationTaster	D	D	D	D	D	D	D
MutationAssessor	M	M	M	H	L	M	L
FATHMM	T	T	D	D	D	D	D
PROVEAN	D	N	D	D	D	D	N
General Prediction
CADD Phred Score	34	24.6	24.2	32	35	26	22.5
ACGS/ACMG Criteria	VUS	VUS	VUS	LP	VUS	VUS	VUS

Abbreviations: gnomAD, Genome Aggregation Database; ExAC, Exome Aggregation Consortium; GERP, Genomic Evolutionary Rate Profiling; CADD, Combined Annotation Dependent Depletion; D, Deleterious; T, tolerated; P, possibly damaging; N, Neutral; U, Unknown; H, high; M, medium; L, low; NR, Not Reported; VUS, Variant of uncertain significance; LP, Likely pathogenic