ClinVar Miner

Submissions for variant NM_033380.3(COL4A5):c.1607G>A (p.Gly536Asp) (rs104886125)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Gharavi Laboratory,Columbia University RCV000684748 SCV000809381 likely pathogenic not provided 2018-09-16 criteria provided, single submitter research
Invitae RCV000684748 SCV001232826 pathogenic not provided 2019-05-04 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 536 of the COL4A5 protein (p.Gly536Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with Alport syndrome (PMID: 17660027, Invitae). ClinVar contains an entry for this variant (Variation ID: 24429). 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.
Research and Development, ARUP Laboratories RCV000021308 SCV000041974 pathogenic Alport syndrome 1, X-linked recessive 2012-12-04 no assertion criteria provided clinical testing Converted during submission to Pathogenic.

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