ClinVar Miner

Submissions for variant NM_033380.3(COL4A5):c.3107G>A (p.Gly1036Glu)

dbSNP: rs104886212
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001377845 SCV001575282 likely pathogenic not provided 2020-06-23 criteria provided, single submitter clinical testing This variant has been observed in individual(s) with clinical features of Alport syndrome (Invitae). 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. 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) This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with glutamic acid at codon 1036 of the COL4A5 protein (p.Gly1036Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid.
GeneDx RCV001377845 SCV001818480 pathogenic not provided 2024-07-15 criteria provided, single submitter clinical testing Affects a glycine residue in a Gly-X-Y motif in the triple helical region of the COL4A5 gene, where the majority of pathogenic missense variants occur, and is predicted to disrupt normal protein folding and function (HGMD; PMID: 10752524); Not observed at significant frequency in large population cohorts (gnomAD); Reported in the heterozygous state in association with renal disease in published literature (PMID: 31328266); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31328266)
Fulgent Genetics, Fulgent Genetics RCV002499779 SCV002782320 pathogenic X-linked Alport syndrome 2021-09-06 criteria provided, single submitter clinical testing

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