ClinVar Miner

Submissions for variant NM_001040108.2(MLH3):c.3658G>A (p.Val1220Met)

gnomAD frequency: 0.00001  dbSNP: rs560775993
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000655389 SCV000777319 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2023-06-23 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 544276). This variant has not been reported in the literature in individuals affected with MLH3-related conditions. This variant is present in population databases (rs560775993, gnomAD 0.01%). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1220 of the MLH3 protein (p.Val1220Met).
Ambry Genetics RCV004025962 SCV002617522 uncertain significance not specified 2024-06-10 criteria provided, single submitter clinical testing The c.3658G>A (p.V1220M) alteration is located in exon 7 (coding exon 6) of the MLH3 gene. This alteration results from a G to A substitution at nucleotide position 3658, causing the valine (V) at amino acid position 1220 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003392504 SCV004119305 uncertain significance MLH3-related disorder 2022-12-29 criteria provided, single submitter clinical testing The MLH3 c.3658G>A variant is predicted to result in the amino acid substitution p.Val1220Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.013% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/14-75500179-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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