ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.850G>C (p.Asp284His)

dbSNP: rs1553412286
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000630150 SCV000751106 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2020-06-09 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with histidine at codon 284 of the MSH6 protein (p.Asp284His). The aspartic acid residue is weakly conserved and there is a moderate physicochemical difference between aspartic acid and histidine. This variant is not present in population databases (ExAC no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with MSH6-related disease.
Color Diagnostics, LLC DBA Color Health RCV000771540 SCV000904099 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with histidine at codon 284 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.
Ambry Genetics RCV000771540 SCV001179103 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-01 criteria provided, single submitter clinical testing The p.D284H variant (also known as c.850G>C), located in coding exon 4 of the MSH6 gene, results from a G to C substitution at nucleotide position 850. The aspartic acid at codon 284 is replaced by histidine, an amino acid with similar properties. This amino acid position is not 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 RCV004002793 SCV004834801 uncertain significance Lynch syndrome 2023-05-15 criteria provided, single submitter clinical testing

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