ClinVar Miner

Submissions for variant NM_000091.5(COL4A3):c.1183G>A (p.Gly395Arg) (rs1574727988)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics,Klinikum rechts der Isar RCV000995725 SCV001150050 likely pathogenic Alport syndrome, autosomal recessive 2018-01-04 criteria provided, single submitter clinical testing
Invitae RCV001238723 SCV001411551 uncertain significance not provided 2019-10-28 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 395 of the COL4A3 protein (p.Gly395Arg). 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 with COL4A3-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Gly395 amino acid residue in COL4A3. Other variant(s) that disrupt this residue have been observed in individuals with COL4A3-related conditions (PMID: 24944784), which suggests that this may be a clinically significant amino acid residue. 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.

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