Submissions for variant NM_000093.5(COL5A1):c.4751G>C (p.Arg1584Pro)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV003397547	SCV004105567	uncertain significance	COL5A1-related disorder	2023-07-03	criteria provided, single submitter	clinical testing	The COL5A1 c.4751G>C variant is predicted to result in the amino acid substitution p.Arg1584Pro. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003759838	SCV004375003	uncertain significance	Ehlers-Danlos syndrome, classic type, 1	2022-12-22	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with COL5A1-related conditions. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COL5A1 protein function. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 1584 of the COL5A1 protein (p.Arg1584Pro).