Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001037359 | SCV001200769 | uncertain significance | Brody myopathy | 2023-08-21 | 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 836273). This variant has not been reported in the literature in individuals affected with ATP2A1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.009%). This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 654 of the ATP2A1 protein (p.Thr654Lys). |
| Illumina Laboratory Services, |
RCV001037359 | SCV001276122 | uncertain significance | Brody myopathy | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Revvity Omics, |
RCV001037359 | SCV003834383 | uncertain significance | Brody myopathy | 2023-06-14 | criteria provided, single submitter | clinical testing | |
| Athena Diagnostics | RCV003482323 | SCV004230044 | uncertain significance | not provided | 2023-08-24 | criteria provided, single submitter | clinical testing | Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity (http://gnomad.broadinstitute.org). Computational tools predict that this variant is damaging. |
| Gene |
RCV003482323 | SCV005334531 | uncertain significance | not provided | 2023-11-29 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |