ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.5494G>T (p.Glu1832Ter)

dbSNP: rs2069382639
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001065163 SCV001230109 pathogenic Neurofibromatosis, type 1 2024-03-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu1811*) 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 clinical features of neurofibromatosis type 1 (PMID: 23913538). ClinVar contains an entry for this variant (Variation ID: 859126). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV004994234 SCV005454587 pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2024-12-03 criteria provided, single submitter clinical testing The p.E1811* pathogenic mutation (also known as c.5431G>T), located in coding exon 37 of the NF1 gene, results from a G to T substitution at nucleotide position 5431. This changes the amino acid from a glutamic acid to a stop codon within coding exon 37. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. In silico splice site analysis predicts that this alteration will result in the creation or strengthening of a novel splice donor site. This variant was identified in 2 of 565 unrelated French probands with clinical diagnoses or suspicion of NF1, and RNA studies demonstrated that this alteration results in an out-of-frame transcript (Sabbagh A et al. Hum Mutat, 2013 Nov;34:1510-8). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this variant is interpreted as a disease-causing mutation.

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