ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.960_964dup (p.Ile322fs)

dbSNP: rs1553648047
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000507246 SCV000601419 likely pathogenic not provided 2016-11-23 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586959 SCV000696193 likely pathogenic Lynch syndrome 2017-02-01 criteria provided, single submitter clinical testing Variant summary: The MLH1 c.960_964dupGAGCA (p.Ile322Argfs) variant results in a premature termination codon, predicted to cause a truncated or absent MLH1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.970delG (p.Glu324fs), c.1210_1211delCT (p.Leu404fs), and c.1381A>T (p.Lys461X)). The variant of interest was not observed in controls (ExAC, 1000 Gs, or ESP), nor has it been, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely pathogenic.
Ambry Genetics RCV002383979 SCV002695694 pathogenic Hereditary cancer-predisposing syndrome 2022-03-11 criteria provided, single submitter clinical testing The c.960_964dupGAGCA pathogenic mutation, located in coding exon 11 of the MLH1 gene, results from a duplication of GAGCA at nucleotide position 960, causing a translational frameshift with a predicted alternate stop codon (p.I322Rfs*47). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc. RCV003449446 SCV004186423 pathogenic Colorectal cancer, hereditary nonpolyposis, type 2 2023-07-18 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

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