ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.5C>T (p.Ser2Leu)

gnomAD frequency: 0.00001  dbSNP: rs752887988
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001039473 SCV001203005 benign Hereditary nonpolyposis colorectal neoplasms 2023-10-30 criteria provided, single submitter clinical testing
Ambry Genetics RCV002354992 SCV002657559 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-15 criteria provided, single submitter clinical testing The p.S2L variant (also known as c.5C>T), located in coding exon 1 of the MSH6 gene, results from a C to T substitution at nucleotide position 5. The serine at codon 2 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV004004727 SCV004832256 uncertain significance Lynch syndrome 2023-08-23 criteria provided, single submitter clinical testing This missense variant replaces serine with leucine at codon 2 of the MSH6 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 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 MSH6-related disorders in the literature. This variant has been identified in 2/244348 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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