ClinVar Miner

Submissions for variant NM_000091.5(COL4A3):c.1831G>A (p.Gly611Arg)

dbSNP: rs1574753929
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München RCV000995728 SCV001150053 pathogenic Autosomal recessive Alport syndrome 2018-11-16 criteria provided, single submitter clinical testing
Invitae RCV001858820 SCV002260519 uncertain significance not provided 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 611 of the COL4A3 protein (p.Gly611Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with COL4A3-related conditions. ClinVar contains an entry for this variant (Variation ID: 807567). 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 expected to disrupt COL4A3 protein function. 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 RCV001858820 SCV004034889 pathogenic not provided 2023-10-30 criteria provided, single submitter clinical testing Affects a glycine residue in a Gly-X-Y motif in the triple helical region of the COL4A3 gene, where the majority of pathogenic missense variants occur, and is predicted to disrupt normal protein folding and function (HGMD; PMID: 10752524); Not observed at significant frequency 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: 32359821, 10752524, 31831576)
Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare RCV001029935 SCV001192731 likely pathogenic Autosomal dominant Alport syndrome 2019-11-17 no assertion criteria provided clinical testing

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