Submissions for variant NM_000093.5(COL5A1):c.1967C>T (p.Pro656Leu)

gnomAD frequency: 0.00013  dbSNP: rs748345448

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV002235485	SCV001011172	likely benign	Ehlers-Danlos syndrome, classic type, 1	2023-12-17	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000869721	SCV001332566	benign	Ehlers-Danlos syndrome, classic type	2018-01-13	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	RCV002235485	SCV002554134	benign	Ehlers-Danlos syndrome, classic type, 1	2022-03-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002271098	SCV002554135	benign	Fibromuscular dysplasia, multifocal	2022-03-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002416038	SCV002722259	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2019-07-23	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
GeneDx	RCV002508271	SCV002817894	uncertain significance	not provided	2022-06-30	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Occurs in the triple helical domain at the X position in the canonical Gly-X-Y repeat; although this variant may have an effect on normal protein folding and function, missense substitution at the X position is not a common mechanism of disease (Symoens et al., 2012; HGMD); This variant is associated with the following publications: (PMID: 22696272)