ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.9_21del (p.Phe3fs)

dbSNP: rs1064795341
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000485543 SCV000571045 pathogenic not provided 2017-06-05 criteria provided, single submitter clinical testing This deletion of 13 nucleotides in MLH1 is denoted c.9_21del13 at the cDNA level and p.Phe3LeufsX10 (F3LfsX10) at the protein level. The surrounding sequence is CGTT[del13]ATTC. The deletion causes a frameshift which changes a Phenylalanine to a Leucine at codon 3, and creates a premature stop codon at position 10 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000539800 SCV000625206 pathogenic Hereditary nonpolyposis colorectal neoplasms 2021-04-30 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MLH1 are known to be pathogenic (PMID: 15713769, 24362816). This variant has not been reported in the literature in individuals with MLH1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Phe3Leufs*10) in the MLH1 gene. It is expected to result in an absent or disrupted protein product.
Myriad Genetics, Inc. RCV003449217 SCV004186095 pathogenic Colorectal cancer, hereditary nonpolyposis, type 2 2023-07-07 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Baylor Genetics RCV003449217 SCV004193021 likely pathogenic Colorectal cancer, hereditary nonpolyposis, type 2 2023-03-01 criteria provided, single submitter clinical testing

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