ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.4078C>T (p.Gln1360Ter)

dbSNP: rs1555617368
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002315793 SCV000663247 pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2017-04-27 criteria provided, single submitter clinical testing The p.Q1360* variant (also known as c.4078C>T), located in coding exon 30 of the NF1 gene, results from a C to T substitution at nucleotide position 4078. This changes the amino acid from a glutamine to a stop codon within coding exon 30. This alteration has been reported in 1 of 565 unrelated patients from the NF-France Network (Sabbagh A et al. Hum. Mutat., 2013 Nov;34:1510-8). 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000756425 SCV000884237 pathogenic not provided 2017-10-10 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001386874 SCV001587265 pathogenic Neurofibromatosis, type 1 2023-06-20 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln1360*) 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 premature translational stop signal has been observed in individual(s) with clinical features of NF1-related conditions (PMID: 23913538, 26556299). ClinVar contains an entry for this variant (Variation ID: 480204). For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV001386874 SCV002560019 pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
GeneDx RCV000756425 SCV002769929 pathogenic not provided 2022-06-22 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26556299, 23913538)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000756425 SCV005624588 pathogenic not provided 2024-04-17 criteria provided, single submitter clinical testing The NF1 c.4078C>T (p.Gln1360*) variant causes the premature termination of NF1 protein synthesis. This variant has been reported in the published literature in individuals affected with neurofibromatosis 1 (PMID: 23913538 (2013)) and a gastrointestinal stromal tumor that showed loss of heterozygosity of the wild-type allele (PMID: 26556299 (2016)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as pathogenic.

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