ClinVar Miner

Submissions for variant NM_033380.3(COL4A5):c.2958_2975del (p.Asp989_Gly994del)

dbSNP: rs1556421106
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000624488 SCV000740784 pathogenic Inborn genetic diseases 2014-12-26 criteria provided, single submitter clinical testing
Invitae RCV001868138 SCV002243851 pathogenic not provided 2021-07-04 criteria provided, single submitter clinical testing This variant, c.2958_2975del, results in the deletion of 6 amino acid(s) of the COL4A5 protein (p.Asp989_Gly994del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with clinical features of Alport syndrome (PMID: 10094548; Invitae). This variant is also known as 3161-3178del (del987-992). ClinVar contains an entry for this variant (Variation ID: 520604). 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). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001868138 SCV003842800 likely pathogenic not provided 2022-09-16 criteria provided, single submitter clinical testing In-frame deletion of six amino acids within the triple helical domain expected to disrupt normal protein folding and function; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign in association with Alport syndrome to our knowledge; This variant is associated with the following publications: (PMID: 28330790)

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