ClinVar Miner

Submissions for variant NM_000553.6(WRN):c.4126C>T (p.Pro1376Ser)

dbSNP: rs1554538654
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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 RCV000633203 SCV000754419 uncertain significance Werner syndrome 2022-10-07 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1376 of the WRN protein (p.Pro1376Ser). This variant is not present in population databases (gnomAD no frequency). 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: 528119). 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 serine 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 RCV002533183 SCV003674600 uncertain significance Inborn genetic diseases 2022-12-15 criteria provided, single submitter clinical testing The c.4126C>T (p.P1376S) alteration is located in exon 34 (coding exon 33) of the WRN gene. This alteration results from a C to T substitution at nucleotide position 4126, causing the proline (P) at amino acid position 1376 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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