Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000522513 | SCV000617861 | pathogenic | not provided | 2020-07-13 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect of protein degradation (Cheng et al., 2011); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 21722859) |
Labcorp Genetics |
RCV000522513 | SCV004295438 | uncertain significance | not provided | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 126 of the DIABLO protein (p.Ser126Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with deafness (PMID: 21722859). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 30449). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects DIABLO function (PMID: 21722859). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
OMIM | RCV000023402 | SCV000044693 | pathogenic | Autosomal dominant nonsyndromic hearing loss 64 | 2011-07-15 | flagged submission | literature only |