ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.114C>T (p.Asn38=) (rs267607706)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000473225 SCV000555990 likely benign Hereditary nonpolyposis colorectal neoplasms 2019-12-31 criteria provided, single submitter clinical testing
Color RCV000579859 SCV000684718 likely benign Hereditary cancer-predisposing syndrome 2016-11-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000579859 SCV001178567 likely benign Hereditary cancer-predisposing syndrome 2019-09-27 criteria provided, single submitter clinical testing In silico models in agreement (benign);Synonymous alterations with insufficient evidence to classify as benign
Integrated Genetics/Laboratory Corporation of America RCV001192577 SCV001360805 likely benign not specified 2019-07-12 criteria provided, single submitter clinical testing Variant summary: MLH1 c.114C>T (p.Asn38Asn) alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 250316 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.114C>T in individuals affected with Hereditary Non-Polyposis Colon Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submissions from other clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.

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