Submissions for variant NM_000093.5(COL5A1):c.3203T>G (p.Val1068Gly)

gnomAD frequency: 0.00008  dbSNP: rs372109796

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000766817	SCV000249813	uncertain significance	not provided	2024-09-17	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis indicates that this missense variant does not alter protein structure/function; 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 (PMID: 22696272; HGMD); This variant is associated with the following publications: (PMID: 22696272)
PreventionGenetics, part of Exact Sciences	RCV000196527	SCV000302190	uncertain significance	not specified	2020-02-19	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002228845	SCV000631486	uncertain significance	Ehlers-Danlos syndrome, classic type, 1	2023-12-17	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 1068 of the COL5A1 protein (p.Val1068Gly). This variant is present in population databases (rs372109796, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of Ehlers-Danlos syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 212956). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000766817	SCV002049243	uncertain significance	not provided	2024-06-04	criteria provided, single submitter	clinical testing	The COL5A1 c.3203T>G; p.Val1068Gly variant (rs372109796), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 212956). This variant is found in the general population with an overall allele frequency of 0.006% (17/282566 alleles) in the Genome Aggregation Database (v2.1.1). Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.472). Due to limited information, the clinical significance of the p.Val1068Gly variant is uncertain at this time.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002277477	SCV002565713	uncertain significance	Ehlers-Danlos syndrome	2019-09-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002321782	SCV002609196	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2023-05-25	criteria provided, single submitter	clinical testing	The p.V1068G variant (also known as c.3203T>G), located in coding exon 40 of the COL5A1 gene, results from a T to G substitution at nucleotide position 3203. The valine at codon 1068 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.