Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
University of Washington Department of Laboratory Medicine, |
RCV000758615 | SCV000887372 | uncertain significance | Lynch syndrome | 2018-05-01 | criteria provided, single submitter | clinical testing | MSH6 NM_000179.2:c.3508A>C has a 14.6% probability of pathogenicity based on combining prior probability from public data with a likelihood ratio of 1.56 to 1, generated from evidence of seeing this as a somatic mutation in a tumor without loss of heterozygosity at the MSH6 locus. See Shirts et al 2018, PMID 29887214. |
All of Us Research Program, |
RCV000758615 | SCV004815844 | uncertain significance | Lynch syndrome | 2023-02-24 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with leucine at codon 1170 of the MSH6 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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 not been identified 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. |