ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.2167G>A (p.Ala723Thr)

gnomAD frequency: 0.00001  dbSNP: rs1392532273
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV000679273 SCV000805967 uncertain significance not provided 2017-02-10 criteria provided, single submitter clinical testing
Invitae RCV001049050 SCV001213084 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2021-11-20 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 560782). This variant has not been reported in the literature in individuals affected with MLH1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 723 of the MLH1 protein (p.Ala723Thr). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.
Color Diagnostics, LLC DBA Color Health RCV001178887 SCV001343451 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-12 criteria provided, single submitter clinical testing
Ambry Genetics RCV001178887 SCV004053404 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-16 criteria provided, single submitter clinical testing The p.A723T variant (also known as c.2167G>A), located in coding exon 19 of the MLH1 gene, results from a G to A substitution at nucleotide position 2167. The alanine at codon 723 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. 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 RCV004004218 SCV004843291 uncertain significance Lynch syndrome 2023-08-25 criteria provided, single submitter clinical testing

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