Submissions for variant NM_000093.5(COL5A1):c.1431G>A (p.Ala477=)

gnomAD frequency: 0.06122  dbSNP: rs61729545

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000124489	SCV000167922	benign	not specified	2013-03-21	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
PreventionGenetics, part of Exact Sciences	RCV000124489	SCV000302138	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000288071	SCV000478529	benign	Ehlers-Danlos syndrome type 7A	2016-06-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001507117	SCV000559962	benign	Ehlers-Danlos syndrome, classic type, 1	2025-02-03	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588822	SCV000695384	benign	not provided	2017-03-15	criteria provided, single submitter	clinical testing	Variant summary: The COL5A1 c.1431G>A (p.Ala477Ala) variant involves the alteration of a nucleotide, resulting in a synonymous change. 5/5 splice prediction tools predict weakening the canonical donor site, however no functional studies confirming effect of this variant on splicing have been published at the time of evaluation. This variant was found in 2210/121094 control chromosomes (208 homozygotes) at a frequency of 0.0182503, which is approximately 14600 times the estimated maximal expected allele frequency of a pathogenic COL5A1 variant (0.0000013), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign.
Ambry Genetics	RCV002312852	SCV000738354	benign	Familial thoracic aortic aneurysm and aortic dissection	2015-04-02	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Illumina Laboratory Services, Illumina	RCV000473739	SCV001330480	benign	Ehlers-Danlos syndrome, classic type	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Genome-Nilou Lab	RCV001507117	SCV002554091	benign	Ehlers-Danlos syndrome, classic type, 1	2022-03-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002269925	SCV002554092	benign	Fibromuscular dysplasia, multifocal	2022-03-15	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000588822	SCV005321002	benign	not provided		criteria provided, single submitter	not provided