Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000529202 | SCV000631063 | uncertain significance | Baller-Gerold syndrome | 2023-12-23 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 696 of the RECQL4 protein (p.Arg696Cys). This variant is present in population databases (rs531970883, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with RECQL4-related conditions. ClinVar contains an entry for this variant (Variation ID: 459374). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RECQL4 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. |
| St. |
RCV001543116 | SCV001761630 | uncertain significance | Rothmund-Thomson syndrome type 2 | 2021-07-22 | criteria provided, single submitter | clinical testing | The RECQL4 c.2086C>T (p.Arg696Cys) missense change has a maximum subpopulation frequency of 0.010% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/8-145739069-G-A). In silico tools are not in agreement about the effect of this variant on protein function, but to our knowledge these predictions have not been confirmed by functional assays. To our knowledge, this variant has not been reported in individuals with RECQL4-associated disorders. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: no criteria met. |
| Ambry Genetics | RCV004023809 | SCV004939221 | uncertain significance | Inborn genetic diseases | 2024-11-30 | criteria provided, single submitter | clinical testing | The p.R696C variant (also known as c.2086C>T), located in coding exon 13 of the RECQL4 gene, results from a C to T substitution at nucleotide position 2086. The arginine at codon 696 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |