ClinVar Miner

Submissions for variant NM_001040108.2(MLH3):c.3637G>A (p.Glu1213Lys)

gnomAD frequency: 0.00014  dbSNP: rs140899869
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001050797 SCV001214922 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2024-11-17 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1213 of the MLH3 protein (p.Glu1213Lys). This variant is present in population databases (rs140899869, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MLH3-related conditions. ClinVar contains an entry for this variant (Variation ID: 847280). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV002268418 SCV002551403 uncertain significance not specified 2024-07-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV002268418 SCV002617755 uncertain significance not specified 2023-09-25 criteria provided, single submitter clinical testing The c.3637G>A (p.E1213K) alteration is located in exon 6 (coding exon 5) of the MLH3 gene. This alteration results from a G to A substitution at nucleotide position 3637, causing the glutamic acid (E) at amino acid position 1213 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005012489 SCV005635759 uncertain significance Endometrial carcinoma; Colorectal cancer, hereditary nonpolyposis, type 7; Colorectal cancer 2024-01-18 criteria provided, single submitter clinical testing

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