ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.1A>T (p.Met1Leu)

dbSNP: rs1060500252
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001939653 SCV002232564 pathogenic Neurofibromatosis, type 1 2021-10-21 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Disruption of the initiator codon has been observed in individuals with neurofibromatosis type 1 (PMID: 23668869, 23913538, 31573083). This variant is not present in population databases (gnomAD no frequency). This sequence change affects the initiator methionine of the NF1 mRNA. The next in-frame methionine is located at codon 68.
Ambry Genetics RCV002423137 SCV002720192 pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2021-08-30 criteria provided, single submitter clinical testing The p.M1? pathogenic mutation (also known as c.1A>T) is located in coding exon 1 of the NF1 gene and results from an A to T substitution at nucleotide position 1. This alters the methionine residue at the initiation codon (ATG). This mutation has been identified in at least one individual with a clinical diagnosis of neurofibromatosis type 1 (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Sequence variations that modify the initiation codon are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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