ClinVar Miner

Submissions for variant NM_000091.5(COL4A3):c.2990G>A (p.Gly997Glu) (rs1553762113)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000667045 SCV000791436 uncertain significance Alport syndrome, autosomal recessive 2017-05-18 criteria provided, single submitter clinical testing
Invitae RCV001226651 SCV001398972 pathogenic not provided 2020-10-11 criteria provided, single submitter clinical testing This sequence change replaces glycine with glutamic acid at codon 997 of the COL4A3 protein (p.Gly997Glu). 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 also been observed to segregate in an autosomal dominant manner in families with clinical features of Alport syndrome (PMID: 25381091, 25596306), and has also described in an individual with autosomal recessive Alport syndrome (PMID: 28542346). ClinVar contains an entry for this variant (Variation ID: 551881). 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. For these reasons, this variant has been classified as Pathogenic.
Precision Medicine Center,Zhengzhou University RCV000667045 SCV001593067 likely pathogenic Alport syndrome, autosomal recessive criteria provided, single submitter research PM1:Located in a mutational hot spot PM2:not found in gnomAD PP1:Cosegregation with disease in multiple affected family members PP3:Multiple lines of computational evidence support a deleterious effect on the gene or gene product

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