ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.196A>G (p.Thr66Ala)

dbSNP: rs876660926
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000220302 SCV000278738 uncertain significance Hereditary cancer-predisposing syndrome 2015-10-07 criteria provided, single submitter clinical testing The p.T66A variant (also known as c.196A>G), located in coding exon 2 of the MLH1 gene, results from an A to G substitution at nucleotide position 196. The threonine at codon 66 is replaced by alanine, an amino acid with similar 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.
PreventionGenetics, part of Exact Sciences RCV000679270 SCV000805961 uncertain significance not provided 2018-01-10 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000220302 SCV000904837 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-04 criteria provided, single submitter clinical testing
Invitae RCV000791827 SCV000931091 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2020-01-18 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with MLH1-related disease. ClinVar contains an entry for this variant (Variation ID: 234208). This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with alanine at codon 66 of the MLH1 protein (p.Thr66Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine.
All of Us Research Program, National Institutes of Health RCV003998607 SCV004835249 uncertain significance Lynch syndrome 2023-03-04 criteria provided, single submitter clinical testing

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