ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.4183C>T (p.Gln1395Ter)

dbSNP: rs1555618494
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000660050 SCV000782010 likely pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV000660050 SCV001209283 pathogenic Neurofibromatosis, type 1 2023-12-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1374*) in the NF1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with neurofibromatosis type 1 (PMID: 23624750, 27838393). ClinVar contains an entry for this variant (Variation ID: 547641). For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV000660050 SCV002560026 pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV003163041 SCV003893750 pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2022-12-08 criteria provided, single submitter clinical testing The p.Q1374* pathogenic mutation (also known as c.4120C>T), located in coding exon 31 of the NF1 gene, results from a C to T substitution at nucleotide position 4120. This changes the amino acid from a glutamine to a stop codon within coding exon 31. This alteration has been identified in individuals with a clinical diagnosis of neurofibromatosis type 1 (Ambry internal data; Campos B et al. Breast Cancer Res Treat, 2013 Jun;139:597-602). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, 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.

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