Submissions for variant NM_001845.6(COL4A1):c.2377G>A (p.Val793Met)

dbSNP: rs769302846

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001887531	SCV002161106	uncertain significance	not provided	2024-12-31	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 793 of the COL4A1 protein (p.Val793Met). This variant is present in population databases (rs769302846, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with COL4A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1396945). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt COL4A1 protein function with a negative predictive value of 95%. 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.
GeneDx	RCV001887531	SCV005437199	uncertain significance	not provided	2024-06-11	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
PreventionGenetics, part of Exact Sciences	RCV004529038	SCV004105651	uncertain significance	COL4A1-related disorder	2024-01-07	no assertion criteria provided	clinical testing	The COL4A1 c.2377G>A variant is predicted to result in the amino acid substitution p.Val793Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0055% of alleles in individuals of East Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.