ClinVar Miner

Submissions for variant NM_033380.3(COL4A5):c.2237G>A (p.Gly746Glu) (rs867625069)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001384770 SCV001584416 pathogenic not provided 2020-01-02 criteria provided, single submitter clinical testing This sequence change replaces glycine with glutamic acid at codon 746 of the COL4A5 protein (p.Gly746Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Alport syndrome (PMID: 24033287, Invitae). ClinVar contains an entry for this variant (Variation ID: 587146). Glycine residues within the Gly-Xaa-Yaa repeats of the triple helix domain are required for the structure and stability of fibrillar collagens (PMID: 7695699, 8218237, 19344236). In COL4A5, missense variants at these glycine residues are significantly enriched in individuals with disease (PMID: 23720012, 27627812) compared to the general population (ExAC). For these reasons, this variant has been classified as Pathogenic.
Precision Medicine Center,Zhengzhou University RCV000714360 SCV001593040 likely pathogenic Alport syndrome 1, X-linked recessive criteria provided, single submitter research PM1:Located in a mutational hot spot PM2:not found in gnomAD PP2:Missense variant in a gene that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease PP3:Multiple lines of computational evidence support a deleterious effect on the gene or gene product
Research and Development, ARUP Laboratories RCV000714360 SCV000845050 pathogenic Alport syndrome 1, X-linked recessive 2018-04-13 no assertion criteria provided literature only

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