ClinVar Miner

Submissions for variant NM_004260.4(RECQL4):c.3545G>A (p.Arg1182His)

gnomAD frequency: 0.00001  dbSNP: rs557256260
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000803501 SCV000943378 uncertain significance Baller-Gerold syndrome 2023-10-04 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1182 of the RECQL4 protein (p.Arg1182His). This variant is present in population databases (rs557256260, 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: 648710). 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 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.
Baylor Genetics RCV001292996 SCV001481720 uncertain significance Rothmund-Thomson syndrome type 2 2019-07-05 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
PreventionGenetics, part of Exact Sciences RCV004538098 SCV004116398 uncertain significance RECQL4-related disorder 2023-07-11 criteria provided, single submitter clinical testing The RECQL4 c.3545G>A variant is predicted to result in the amino acid substitution p.Arg1182His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.011% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-145736896-C-T) and has been interpreted as uncertain in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/648710/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV001292996 SCV005689258 uncertain significance Rothmund-Thomson syndrome type 2 2024-09-16 criteria provided, single submitter clinical testing The RECQL4 c.3545G>A (p.Arg1182His) missense change has a maximum subpopulation frequency of 0.01% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). In silico tools are inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in individuals with RECQL4-associated conditions. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.

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