ClinVar Miner

Submissions for variant NM_000553.6(WRN):c.3230C>T (p.Pro1077Leu)

gnomAD frequency: 0.00005  dbSNP: rs751843882
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000814548 SCV000954961 uncertain significance Werner syndrome 2024-08-21 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1077 of the WRN protein (p.Pro1077Leu). This variant is present in population databases (rs751843882, gnomAD 0.04%), including at least one homozygous and/or hemizygous individual. 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: 657848). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (internal data). 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.

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