ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.113A>C (p.Asn38Thr)

dbSNP: rs587778888
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
University of Washington Department of Laboratory Medicine, University of Washington RCV000758567 SCV000887307 pathogenic Lynch syndrome 2018-05-01 criteria provided, single submitter clinical testing MLH1 NM_000249.3:c.113A>C has a 99.6% probability of pathogenicity based on combining prior probability from public data with a likelihood ratio of 26.5 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.
Ambry Genetics RCV002458360 SCV002614289 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-19 criteria provided, single submitter clinical testing The p.N38T variant (also known as c.113A>C), located in coding exon 1 of the MLH1 gene, results from an A to C substitution at nucleotide position 113. The asparagine at codon 38 is replaced by threonine, an amino acid with similar properties. This alteration has been detected as somatic in a colorectal cancer in conjunction with loss of heterozygosity of MLH1 (Shirts BH et al. Am J Hum Genet. 2018 Jul 5;103(1):19-29). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. In addition, this alteration is predicted to be deleterious by MAPP-MMR in silico analyses (Chao EC et al. Hum. Mutat. 2008 Jun;29:852-60). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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