ClinVar Miner

Submissions for variant NM_000553.6(WRN):c.2509A>G (p.Ile837Val)

gnomAD frequency: 0.00001  dbSNP: rs762233119
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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 RCV001970345 SCV002247998 uncertain significance Werner syndrome 2022-07-19 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 837 of the WRN protein (p.Ile837Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs762233119, gnomAD 0.0009%). 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: 1467191). 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.
Ambry Genetics RCV004970663 SCV005533745 uncertain significance Inborn genetic diseases 2024-11-12 criteria provided, single submitter clinical testing The c.2509A>G (p.I837V) alteration is located in exon 21 (coding exon 20) of the WRN gene. This alteration results from a A to G substitution at nucleotide position 2509, causing the isoleucine (I) at amino acid position 837 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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