Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000655020 | SCV000776940 | likely pathogenic | Dilated cardiomyopathy 1II | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 109 of the CRYAB protein (p.Asp109Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant restrictive cardiomyopathy (PMID: 28493373). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 265829). 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 CRYAB function (PMID: 28493373). This variant disrupts the p.Asp109 amino acid residue in CRYAB. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21920752, 23194663, 26627873). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Institut für Laboratoriums- |
RCV000491328 | SCV000298148 | pathogenic | Cardiomyopathy, familial restrictive, 1 | 2016-05-01 | no assertion criteria provided | clinical testing |