ClinVar Miner

Submissions for variant NM_002528.7(NTHL1):c.11T>A (p.Leu4Ter)

dbSNP: rs1413587495
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001909047 SCV002172708 pathogenic not provided 2024-09-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu12*) in the NTHL1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NTHL1 are known to be pathogenic (PMID: 25938944, 26559593). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NTHL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1403427). For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc. RCV003458235 SCV004188384 pathogenic Familial adenomatous polyposis 3 2023-08-31 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Ambry Genetics RCV004945782 SCV005460402 uncertain significance Hereditary cancer-predisposing syndrome 2024-11-12 criteria provided, single submitter clinical testing The p.L12* variant (also known as c.35T>A), located in coding exon 1 of the NTHL1 gene, results from a T to A substitution at nucleotide position 35. This changes the amino acid from a leucine to a stop codon within coding exon 1. The predicted stop codon occurs in the 5’ end of theNTHL1 gene. Premature termination codons in the 5’ end of a gene have been reported to escape nonsense-mediated mRNAdecay and/or lead to re-initiation (Rivas et al. Science. 2015 May 8;348(6235):666-9; Lindeboom et al. Nat Genet. 2016 Oct;48(10):1112-8; Rhee et al. Sci Rep. 2017 May 10;7(1):1653). The exact functional effect of this alteration is unknown. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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