ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.25C>G (p.Arg9Gly)

dbSNP: rs587779000
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001177312 SCV001341506 uncertain significance Hereditary cancer-predisposing syndrome 2021-02-15 criteria provided, single submitter clinical testing This missense variant replaces arginine with glycine at codon 9 of the MLH1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with MMR-deficient colorectal cancer who also has a pathogenic APC variant (PMID: 32635641). 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.
Invitae RCV002559722 SCV003017732 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2022-03-19 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 919271). This variant has not been reported in the literature in individuals affected with MLH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 9 of the MLH1 protein (p.Arg9Gly).
Baylor Genetics RCV003473722 SCV004195016 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 2 2023-10-31 criteria provided, single submitter clinical testing

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