Total submissions: 3
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. |
Gene |
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) |