Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001240656 | SCV001413622 | uncertain significance | not provided | 2024-05-26 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 321 of the RECQL protein (p.Cys321Tyr). This variant is present in population databases (rs150889040, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. 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: 966068). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RECQL protein function with a positive predictive value of 80%. 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 |
RCV001240656 | SCV001767303 | uncertain significance | not provided | 2024-04-24 | criteria provided, single submitter | clinical testing | Observed in an individual with ovarian cancer who also carried a pathogenic RAD51D variant (PMID: 28591191); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (PMID: 25741868); This variant is associated with the following publications: (PMID: 27248010, 19151156, 28591191, 33471991) |
| Ambry Genetics | RCV004034655 | SCV002689027 | uncertain significance | not specified | 2024-10-06 | criteria provided, single submitter | clinical testing | The p.C321Y variant (also known as c.962G>A), located in coding exon 8 of the RECQL gene, results from a G to A substitution at nucleotide position 962. The cysteine at codon 321 is replaced by tyrosine, an amino acid with highly dissimilar properties. This variant has been identified in an individual diagnosed with ovarian cancer (Stafford JL et al. PLoS ONE, 2017 Jun;12:e0178450). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Prevention |
RCV003414044 | SCV004113882 | uncertain significance | RECQL-related disorder | 2022-10-04 | criteria provided, single submitter | clinical testing | The RECQL c.962G>A variant is predicted to result in the amino acid substitution p.Cys321Tyr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.13% of alleles in individuals of Ashkenazi Jewish descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-21628746-C-T) and has been reported as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/966068). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001240656 | SCV004220244 | likely benign | not provided | 2022-11-30 | criteria provided, single submitter | clinical testing |