ClinVar Miner

Submissions for variant NM_000092.5(COL4A4):c.1441G>A (p.Gly481Ser)

gnomAD frequency: 0.00001  dbSNP: rs181528936
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000710831 SCV000841136 pathogenic not provided 2019-06-13 criteria provided, single submitter clinical testing The variant disrupts a glycine residue in the canonical Gly-X-Y repeats of the triple helix domain, which are required for stability and structure of this protein. Therefore it is expected to severely affect the function of the protein. Found in at least one symptomatic patient, and found in general population data that is consistent with pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp RCV000710831 SCV001555249 benign not provided 2023-09-29 criteria provided, single submitter clinical testing
GeneDx RCV000710831 SCV001981930 uncertain significance not provided 2024-05-09 criteria provided, single submitter clinical testing Affects a glycine residue in a Gly-X-Y motif in the triple helical region of the COL4A4 gene; 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: 15618242, 34400539)
Revvity Omics, Revvity RCV000710831 SCV002023307 uncertain significance not provided 2022-11-30 criteria provided, single submitter clinical testing
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV000710831 SCV002061443 uncertain significance not provided 2021-07-20 criteria provided, single submitter clinical testing PP3, PM1, PM2
PreventionGenetics, part of Exact Sciences RCV004535760 SCV004724626 pathogenic COL4A4-related disorder 2024-02-16 criteria provided, single submitter clinical testing The COL4A4 c.1441G>A variant is predicted to result in the amino acid substitution p.Gly481Ser. This variant affects a glycine (Gly) residue of the conserved triple helical domain (residues 65-1459) of the COL4A4 protein (uniprot.org), where substitutions of the glycine (Gly) residue are usually pathogenic (Hudson et al. 1993. PubMed ID: 8253711; https://www.ncbi.nlm.nih.gov/books/NBK1207/). This variant has been reported in an individual with macroscopic haematuria with microhaematuria and her affected mother (Frasca et al. 2005. PubMed ID: 15618242). This variant is reported in 0.061% of alleles in individuals of Latino descent in gnomAD. This variant is interpreted as pathogenic.

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