Total submissions: 4
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, |
RCV003237788 | SCV002011297 | uncertain significance | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
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. |
Prevention |
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. |