ClinVar Miner

Submissions for variant NM_000093.5(COL5A1):c.3874G>A (p.Glu1292Lys)

dbSNP: rs1319735007
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002241582 SCV001401140 pathogenic Ehlers-Danlos syndrome, classic type, 1 2024-02-14 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1292 of the COL5A1 protein (p.Glu1292Lys). RNA analysis indicates that this missense change induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with classic Ehlers-Danlos syndrome (PMID: 19370768, 22696272). ClinVar contains an entry for this variant (Variation ID: 955996). 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 with a negative predictive value of 95%. Studies have shown that this missense change results in activation of a cryptic splice site and introduces a premature termination codon (PMID: 19370768). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV003328478 SCV004035140 likely pathogenic Ehlers-Danlos syndrome, classic type 2023-09-18 criteria provided, single submitter clinical testing

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