ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.3044T>C (p.Leu1015Pro)

dbSNP: rs1131691112
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002311236 SCV000581316 pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2023-10-16 criteria provided, single submitter clinical testing The p.L1015P pathogenic mutation (also known as c.3044T>C), located in coding exon 23 of the NF1 gene, results from a T to C substitution at nucleotide position 3044. The leucine at codon 1015 is replaced by proline, an amino acid with similar properties. This alteration has been detected in several individuals reported to fulfill NF1 clinical diagnostic criteria (Kluwe L, et al. Hum. Mutat. 2003 Nov; 22(5):420; Evans DG et al. EBioMedicine. 2016 May;7:212-20; external communication; Amby internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp RCV001379172 SCV001576923 pathogenic Neurofibromatosis, type 1 2025-02-02 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1015 of the NF1 protein (p.Leu1015Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with neurofibromatosis type 1 (PMID: 14517963, 27322474; internal data). ClinVar contains an entry for this variant (Variation ID: 428992). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt NF1 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV001379172 SCV002561826 likely pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing

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