ClinVar Miner

Submissions for variant NM_000092.5(COL4A4):c.3875G>A (p.Gly1292Asp)

dbSNP: rs971779449
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002298753 SCV002597986 uncertain significance not provided 2025-01-03 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 1292 of the COL4A4 protein (p.Gly1292Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with COL4A4-related conditions (PMID: 34400539). ClinVar contains an entry for this variant (Variation ID: 599122). 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 expected to disrupt COL4A4 protein function with a positive 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 RCV002298753 SCV005396491 likely pathogenic not provided 2024-05-06 criteria provided, single submitter clinical testing Identified in a patient with hematuria in published literature (PMID: 34400539); Affects a glycine residue in a Gly-X-Y motif in the triple helical region of the COL4A4 gene, where the majority of pathogenic missense variants occur, and is predicted to disrupt normal protein folding and function (HGMD; PMID: 10752524); Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 10752524, 34400539)
Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare RCV000735720 SCV000863873 likely pathogenic Autosomal dominant Alport syndrome 2018-05-17 no assertion criteria provided clinical testing

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