ClinVar Miner

Submissions for variant NM_000553.6(WRN):c.2131C>T (p.Arg711Trp)

gnomAD frequency: 0.00017  dbSNP: rs34560788
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000228524 SCV000285534 likely benign Werner syndrome 2024-01-19 criteria provided, single submitter clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV003237788 SCV002011297 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV001818575 SCV002071492 uncertain significance not specified 2021-10-19 criteria provided, single submitter clinical testing DNA sequence analysis of the WRN gene demonstrated a sequence change, c.2131C>T, in exon 19 that results in an amino acid change, p.Arg711Trp. This sequence change does not appear to have been previously described in individuals with WRN-related disorders. This sequence change has been described in the gnomAD database with a low frequency of 0.040% in the non-Finnish European subpopulation (dbSNP rs34560788). The p.Arg711Trp change affects a highly conserved amino acid residue located in a domain of the WRN protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Arg711Trp substitution. Due to insufficient evidence and the lack of functional studies, the clinical significance of the p.Arg711Trp change remains unknown at this time.
PreventionGenetics, part of Exact Sciences RCV003967619 SCV004794859 uncertain significance WRN-related condition 2023-11-10 criteria provided, single submitter clinical testing The WRN c.2131C>T variant is predicted to result in the amino acid substitution p.Arg711Trp. This variant was reported in a cohort study of patients with dyslipidemia and other metabolic phenotypes (Table S4, Dron et al 2020. PubMed ID: 32041611). This variant is reported in 0.040% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-30969173-C-T) and has conflicting interpretations regarding its pathogenicity in ClinVar, ranging from likely benign to uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/238136/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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