Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001227239 | SCV001399589 | uncertain significance | not provided | 2024-10-29 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 619 of the RECQL protein (p.Asn619His). This variant is present in population databases (rs762888181, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with RECQL-related conditions. ClinVar contains an entry for this variant (Variation ID: 954727). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
Gene |
RCV001227239 | SCV002818638 | uncertain significance | not provided | 2022-07-06 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV004601409 | SCV003879094 | likely benign | not specified | 2024-03-29 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001227239 | SCV004220212 | uncertain significance | not provided | 2023-06-20 | criteria provided, single submitter | clinical testing | To the best of our knowledge, the variant has not been reported in the published literature. The frequency of this variant in the general population, 0.0004 (13/32264 chromosomes in Latino/Admixed American subpopulation, http://gnomad.broadinstitute.org), is higher than would generally be expected for pathogenic variants in this gene. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |