ClinVar Miner

Submissions for variant NM_001040108.2(MLH3):c.443T>C (p.Val148Ala)

gnomAD frequency: 0.00003  dbSNP: rs1484161045
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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 RCV000817202 SCV000957751 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2018-07-12 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 output the following: SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with MLH3-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with alanine at codon 148 of the MLH3 protein (p.Val148Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine.
Ambry Genetics RCV004028906 SCV002632589 uncertain significance not specified 2024-01-02 criteria provided, single submitter clinical testing The c.443T>C (p.V148A) alteration is located in exon 2 (coding exon 1) of the MLH3 gene. This alteration results from a T to C substitution at nucleotide position 443, causing the valine (V) at amino acid position 148 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002478904 SCV002778650 uncertain significance Endometrial carcinoma; Colorectal cancer, hereditary nonpolyposis, type 7; Colorectal cancer 2022-02-21 criteria provided, single submitter clinical testing

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