Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000204219 | SCV000260550 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2023-12-23 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000216919 | SCV000274303 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-21 | criteria provided, single submitter | clinical testing | The p.T216I variant (also known as c.647C>T), located in coding exon 4 of the MSH6 gene, results from a C to T substitution at nucleotide position 647. The threonine at codon 216 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000588780 | SCV000695922 | uncertain significance | not provided | 2017-06-16 | criteria provided, single submitter | clinical testing | Variant summary: The MSH6 c.647C>T (p.Thr216Ile) variant involves the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant. This variant was found in 1/119058 control chromosomes at a frequency of 0.0000084, which does not exceed the estimated maximal expected allele frequency of a pathogenic MSH6 variant (0.0001421). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available. |
Color Diagnostics, |
RCV000216919 | SCV000908353 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-14 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with isoleucine at codon 216 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 been identified in 2/247374 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000588780 | SCV002046388 | uncertain significance | not provided | 2020-11-11 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV003997621 | SCV004841182 | uncertain significance | Lynch syndrome | 2023-10-30 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with isoleucine at codon 216 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 hereditary cancer in the literature. This variant has been identified in 2/247374 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. |