Submissions for variant NM_000553.6(WRN):c.830A>C (p.Asn277Thr)

gnomAD frequency: 0.00001  dbSNP: rs749379604

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001918375	SCV002181968	uncertain significance	Werner syndrome	2022-04-08	criteria provided, single submitter	clinical testing	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 sequence change replaces asparagine, which is neutral and polar, with threonine, which is neutral and polar, at codon 277 of the WRN protein (p.Asn277Thr). This variant has not been reported in the literature in individuals affected with WRN-related conditions. 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. 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 threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function.
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University	RCV003154048	SCV003843536	benign	Ovarian cancer	2022-01-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV001918375	SCV005676826	uncertain significance	Werner syndrome	2024-02-29	criteria provided, single submitter	clinical testing