ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.1897-7C>T

gnomAD frequency: 0.00001  dbSNP: rs373078652
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000461885 SCV000543591 likely benign Hereditary nonpolyposis colorectal neoplasms 2024-01-05 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV000758581 SCV000887326 uncertain significance Lynch syndrome 2018-05-01 criteria provided, single submitter clinical testing MLH1 NM_000249.3:c.1897-7C>T has a 7.8% probability of pathogenicity based on combining prior probability from public data with a likelihood ratio of 0.16 to 1, generated from evidence of seeing this as a somatic mutation in a tumor with loss of heterozygosity at the MLH1 locus. See Shirts et al 2018, PMID 29887214.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759811 SCV000889391 uncertain significance not provided 2022-11-08 criteria provided, single submitter clinical testing The frequency of this variant in the general population, 0.000004 (1/251320 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in the somatic state in a tumor sample (PMID: 29887214 (2018)). Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on MLH1 mRNA splicing yielded predictions that this variant may result in the gain of a cryptic splice site without affecting the natural splice sites . Based on the available information, we are unable to determine the clinical significance of this variant.
Color Diagnostics, LLC DBA Color Health RCV001189941 SCV001357337 likely benign Hereditary cancer-predisposing syndrome 2020-12-07 criteria provided, single submitter clinical testing
GeneDx RCV000759811 SCV001833110 likely benign not provided 2019-05-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV001189941 SCV002722557 likely benign Hereditary cancer-predisposing syndrome 2020-04-09 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GenomeConnect - Invitae Patient Insights Network RCV001535615 SCV001749636 not provided Hereditary nonpolyposis colon cancer no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 12-23-2016 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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