ClinVar Miner

Submissions for variant NM_033380.3(COL4A5):c.2183G>A (p.Gly728Glu)

dbSNP: rs1603292422
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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 RCV001377446 SCV001574778 likely pathogenic not provided 2020-09-01 criteria provided, single submitter clinical testing 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 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). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt COL4A5 protein function. This variant has not been reported in the literature in individuals with COL4A5-related conditions. ClinVar contains an entry for this variant (Variation ID: 635479). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with glutamic acid at codon 728 of the COL4A5 protein (p.Gly728Glu). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and glutamic acid.
Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn RCV000786939 SCV005387749 likely pathogenic X-linked Alport syndrome 2024-02-06 criteria provided, single submitter clinical testing
Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare RCV000786939 SCV000925843 likely pathogenic X-linked Alport syndrome 2019-02-04 no assertion criteria provided clinical testing

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