Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002048146 | SCV002288993 | uncertain significance | Dilated cardiomyopathy 1II | 2021-12-09 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with CRYAB-related conditions. This variant is present in population databases (rs781915800, gnomAD 0.003%). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 121 of the CRYAB protein (p.Lys121Arg). |
| Fulgent Genetics, |
RCV002492345 | SCV002800719 | uncertain significance | Myofibrillar myopathy 2; Cataract 16 multiple types; Fatal infantile hypertonic myofibrillar myopathy; Dilated cardiomyopathy 1II | 2021-09-30 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004046228 | SCV005017976 | uncertain significance | Cardiovascular phenotype | 2023-11-26 | criteria provided, single submitter | clinical testing | The p.K121R variant (also known as c.362A>G), located in coding exon 3 of the CRYAB gene, results from an A to G substitution at nucleotide position 362. The lysine at codon 121 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |