Submissions for variant NM_001042492.3(NF1):c.968C>A (p.Ala323Asp)

dbSNP: rs2066507556

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001041575	SCV001205199	pathogenic	Neurofibromatosis, type 1	2022-09-01	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 323 of the NF1 protein (p.Ala323Asp). This missense change has been observed in individual(s) with neurofibromatosis type 1 (PMID: 30308447). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 839743). 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. For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center	RCV001041575	SCV004812128	likely pathogenic	Neurofibromatosis, type 1	2024-03-21	criteria provided, single submitter	clinical testing	Criteria applied: PS4_MOD,PS2,PM2,PP3,PP4
Laboratory of Medical Genetics, National & Kapodistrian University of Athens	RCV001041575	SCV001548425	likely pathogenic	Neurofibromatosis, type 1	2019-01-01	no assertion criteria provided	clinical testing