ClinVar Miner

Submissions for variant NM_000553.6(WRN):c.587G>A (p.Arg196His)

gnomAD frequency: 0.00002  dbSNP: rs561603992
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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 RCV000633190 SCV000754405 uncertain significance Werner syndrome 2024-11-18 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 196 of the WRN protein (p.Arg196His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 135446). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Fulgent Genetics, Fulgent Genetics RCV000633190 SCV005676822 uncertain significance Werner syndrome 2024-06-18 criteria provided, single submitter clinical testing
ITMI RCV000122303 SCV000086532 not provided not specified 2013-09-19 no assertion provided reference population
PreventionGenetics, part of Exact Sciences RCV004748591 SCV005347085 uncertain significance WRN-related disorder 2024-03-21 no assertion criteria provided clinical testing The WRN c.587G>A variant is predicted to result in the amino acid substitution p.Arg196His. This variant was reported in a cohort study of healthy adults with no personal or family history indicative of a highly penetrant, cancer-predisposing variant (Supp. Table 1 in Bodian DL et al 2014. PubMed ID: 24728327. This variant is reported in 0.0046% of alleles in individuals of European (non-Finnish) descent in gnomAD and has been reported as uncertain in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/135446/). 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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