ClinVar Miner

Submissions for variant NM_033380.3(COL4A5):c.3437G>A (p.Gly1146Glu)

dbSNP: rs2068061224
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001050800 SCV001214925 likely pathogenic not provided 2021-07-17 criteria provided, single submitter clinical testing This variant disrupts the triple helix domain of COL4A5. 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). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant has been observed in individual(s) with clinical features of Alport syndrome (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with glutamic acid at codon 1146 of the COL4A5 protein (p.Gly1146Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid.
Medical Genetics, University of Parma RCV001089924 SCV001245125 likely pathogenic X-linked Alport syndrome 2020-03-11 criteria provided, single submitter clinical testing

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