ClinVar Miner

Submissions for variant NM_000251.3(MSH2):c.928C>T (p.Leu310Phe)

dbSNP: rs750866402
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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 RCV002010990 SCV002291163 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2023-06-28 criteria provided, single submitter clinical testing 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. This variant disrupts the p.Leu310 amino acid residue in MSH2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22290698, 30374176). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MSH2 protein function. ClinVar contains an entry for this variant (Variation ID: 1502458). This missense change has been observed in individual(s) with breast cancer (PMID: 28975465). This variant is present in population databases (no rsID available, gnomAD 0.001%). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 310 of the MSH2 protein (p.Leu310Phe).
Color Diagnostics, LLC DBA Color Health RCV003585188 SCV004356642 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-20 criteria provided, single submitter clinical testing This missense variant replaces leucine with phenylalanine at codon 310 of the MSH2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/230146 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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