Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Blueprint Genetics | RCV000208522 | SCV000263816 | uncertain significance | Primary dilated cardiomyopathy | 2015-01-08 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000805399 | SCV000945353 | uncertain significance | Dilated cardiomyopathy 1II | 2023-07-03 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.Arg11 amino acid residue in CRYAB. Other variant(s) that disrupt this residue have been observed in individuals with CRYAB-related conditions (PMID: 19597569), which suggests that this may be a clinically significant amino acid residue. 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. ClinVar contains an entry for this variant (Variation ID: 222531). This missense change has been observed in individual(s) with autosomal recessive congenital cataracts (PMID: 26402864). It has also been observed to segregate with disease in related individuals. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 11 of the CRYAB protein (p.Arg11Cys). |