Submissions for variant NM_001042492.3(NF1):c.970T>C (p.Cys324Arg)

dbSNP: rs199474735

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001060875	SCV001225591	likely pathogenic	Neurofibromatosis, type 1	2022-10-27	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of neurofibromatosis type I (PMID: 15060124; Invitae). ClinVar contains an entry for this variant (Variation ID: 68365). 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. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 324 of the NF1 protein (p.Cys324Arg).
UniProtKB/Swiss-Prot	RCV000059219	SCV000090748	not provided	not provided		no assertion provided	not provided