ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.389del (p.Tyr130fs)

dbSNP: rs587779012
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000075694 SCV000106698 pathogenic Lynch syndrome 2013-09-05 reviewed by expert panel research Coding sequence variation resulting in a stop codon
Ambry Genetics RCV002354261 SCV002620931 pathogenic Hereditary cancer-predisposing syndrome 2014-12-13 criteria provided, single submitter clinical testing The c.389delA pathogenic mutation, located in coding exon 5 of the MLH1 gene, results from a deletion of one nucleotide at nucleotide position 389, causing a translational frameshift with a predicted alternate stop codonp (T130Sfs*6). Since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Myriad Genetics, Inc. RCV003451144 SCV004186575 pathogenic Colorectal cancer, hereditary nonpolyposis, type 2 2023-07-13 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Invitae RCV003593885 SCV004364991 pathogenic Hereditary nonpolyposis colorectal neoplasms 2023-12-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr130Serfs*6) in the MLH1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MLH1 are known to be pathogenic (PMID: 15713769, 24362816). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MLH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 90206). For these reasons, this variant has been classified as Pathogenic.

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