ClinVar Miner

Submissions for variant NM_000553.6(WRN):c.1457C>T (p.Thr486Met)

gnomAD frequency: 0.00001  dbSNP: rs761328537
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000633235 SCV000754451 uncertain significance Werner syndrome 2024-10-22 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 486 of the WRN protein (p.Thr486Met). This variant is present in population databases (rs761328537, 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: 528152). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The methionine 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.
Fulgent Genetics, Fulgent Genetics RCV000633235 SCV002781748 uncertain significance Werner syndrome 2024-06-22 criteria provided, single submitter clinical testing
Ambry Genetics RCV002533184 SCV003745426 uncertain significance Inborn genetic diseases 2021-08-23 criteria provided, single submitter clinical testing The c.1457C>T (p.T486M) alteration is located in exon 12 (coding exon 11) of the WRN gene. This alteration results from a C to T substitution at nucleotide position 1457, causing the threonine (T) at amino acid position 486 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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