ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.139T>C (p.Ser47Pro)

dbSNP: rs2143626487
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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 RCV001385884 SCV001585894 pathogenic Neurofibromatosis, type 1 2023-10-28 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 47 of the NF1 protein (p.Ser47Pro). 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: 27322474, 27716896). ClinVar contains an entry for this variant (Variation ID: 1073012). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae 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.
Ambry Genetics RCV004995730 SCV005459611 likely pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2024-11-07 criteria provided, single submitter clinical testing The p.S47P variant (also known as c.139T>C), located in coding exon 2 of the NF1 gene, results from a T to C substitution at nucleotide position 139. The serine at codon 47 is replaced by proline, an amino acid with similar properties. This variant has been reported in multiple individuals with features consistent with neurofibromatosis type 1 (NF1) (Evans DG et al. EBioMedicine, 2016 May;7:212-20; Cassiman C et al. Clin Genet, 2017 Apr;91:529-535). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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