ClinVar Miner

Submissions for variant NM_000553.6(WRN):c.2371T>G (p.Cys791Gly)

gnomAD frequency: 0.00003  dbSNP: rs200169079
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000633189 SCV000754404 uncertain significance Werner syndrome 2022-10-27 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with glycine, which is neutral and non-polar, at codon 791 of the WRN protein (p.Cys791Gly). This variant is present in population databases (rs200169079, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with WRN-related conditions. ClinVar contains an entry for this variant (Variation ID: 528106). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). 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.
Genetic Services Laboratory, University of Chicago RCV001821792 SCV002068991 uncertain significance not specified 2021-12-17 criteria provided, single submitter clinical testing DNA sequence analysis of the WRN gene demonstrated a sequence change, c.2371T>G, in exon 20 that results in an amino acid change, p.Cys791Gly. This sequence change has been described in the gnomAD database with a frequency of 0.011% in the non-Finnish European subpopulation (dbSNP rs200169079). The p.Cys791Gly 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.Cys791Gly substitution. This sequence change does not appear to have been previously described in individuals with WRN-related disorders. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Cys791Gly change remains unknown at this time.

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