ClinVar Miner

Submissions for variant NM_000091.5(COL4A3):c.1364G>T (p.Gly455Val)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002282964 SCV002571096 uncertain significance not specified 2022-07-08 criteria provided, single submitter clinical testing Variant summary: COL4A3 c.1364G>T (p.Gly455Val) results in a non-conservative amino acid change located in the Collagen triple helix repeat (IPR008160) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 249426 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1364G>T in individuals affected with Alport Syndrome, Autosomal Recessive and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
CeGaT Center for Human Genetics Tuebingen RCV002511152 SCV002821040 likely pathogenic not provided 2022-11-01 criteria provided, single submitter clinical testing COL4A3: PM1:Strong, PM2, PM5
PreventionGenetics, part of Exact Sciences RCV003403775 SCV004103967 likely pathogenic COL4A3-related disorder 2023-10-02 criteria provided, single submitter clinical testing The COL4A3 c.1364G>T variant is predicted to result in the amino acid substitution p.Gly455Val. The p.Gly455 residue is located in the conserved triple helical domain, where substitutions of the glycine are usually pathogenic (UniProt residues 43-1438, Hudson et al. 1993. PubMed ID: 8253711; https://www.ncbi.nlm.nih.gov/books/NBK21582/). A different substitution of this amino acid (p.Gly455Cys) has been reported in a study of individuals with hematuric nephropathy (Morinière et al 2014. PubMed ID: 24854265). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as likely pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005017183 SCV005648977 likely pathogenic Autosomal dominant Alport syndrome; Hematuria, benign familial, 2; Alport syndrome 3b, autosomal recessive 2024-01-08 criteria provided, single submitter clinical testing

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