Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001349060 | SCV001543387 | uncertain significance | Dilated cardiomyopathy 1II | 2023-09-15 | 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. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 1044759). This variant has not been reported in the literature in individuals affected with CRYAB-related conditions. 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 proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 13 of the CRYAB protein (p.Pro13Thr). |
Gene |
RCV001799760 | SCV002043912 | uncertain significance | not provided | 2021-06-24 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported in ClinVar but additional evidence is not available (ClinVar Variant ID#1044759; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 27535533) |
Ambry Genetics | RCV002357199 | SCV002622252 | uncertain significance | Cardiovascular phenotype | 2023-07-01 | criteria provided, single submitter | clinical testing | The p.P13T variant (also known as c.37C>A), located in coding exon 1 of the CRYAB gene, results from a C to A substitution at nucleotide position 37. The proline at codon 13 is replaced by threonine, 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. |
Fulgent Genetics, |
RCV002486434 | SCV002789447 | uncertain significance | Myofibrillar myopathy 2; Cataract 16 multiple types; Fatal infantile hypertonic myofibrillar myopathy; Dilated cardiomyopathy 1II | 2021-09-20 | criteria provided, single submitter | clinical testing |