ClinVar Miner

Submissions for variant NM_000553.6(WRN):c.4145G>A (p.Cys1382Tyr)

gnomAD frequency: 0.00003  dbSNP: rs761450405
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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 RCV001224136 SCV001396319 uncertain significance Werner syndrome 2024-05-28 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 1382 of the WRN protein (p.Cys1382Tyr). This variant is present in population databases (rs761450405, 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: 952090). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The tyrosine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 RCV004963243 SCV005533744 uncertain significance Inborn genetic diseases 2024-10-07 criteria provided, single submitter clinical testing The c.4145G>A (p.C1382Y) alteration is located in exon 34 (coding exon 33) of the WRN gene. This alteration results from a G to A substitution at nucleotide position 4145, causing the cysteine (C) at amino acid position 1382 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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