Submissions for variant NM_001042492.3(NF1):c.7010T>C (p.Leu2337Pro)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003494747	SCV004296801	pathogenic	Neurofibromatosis, type 1	2023-05-14	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Leu231 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 31730495). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. This missense change has been observed in individual(s) with neurofibromatosis type 1 (PMID: 27322474). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 2316 of the NF1 protein (p.Leu2316Pro).