Submissions for variant NM_000393.5(COL5A2):c.3316C>T (p.Arg1106Trp)

gnomAD frequency: 0.00119  dbSNP: rs146789395

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001705105	SCV000250019	likely benign	not provided	2020-10-19	criteria provided, single submitter	clinical testing	Occurs in the triple helical domain at the Y 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 Y position is not a common mechanism of disease (Symoens et al., 2012; Stenson et al., 2014)
Illumina Laboratory Services, Illumina	RCV000333952	SCV000425626	likely benign	Ehlers-Danlos syndrome type 7A	2016-06-14	criteria provided, single submitter	clinical testing
Invitae	RCV000475732	SCV000558989	benign	Ehlers-Danlos syndrome, classic type, 1	2024-01-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002315575	SCV000738696	likely benign	Familial thoracic aortic aneurysm and aortic dissection	2022-01-20	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000659484	SCV000781299	uncertain significance	Connective tissue disorder	2016-11-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001141923	SCV001302310	benign	Ehlers-Danlos syndrome, classic type, 2	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.