Submissions for variant NM_001042492.3(NF1):c.278G>A (p.Cys93Tyr)

gnomAD frequency: 0.00001  dbSNP: rs199474728

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000466535	SCV000542011	pathogenic	Neurofibromatosis, type 1	2023-08-18	criteria provided, single submitter	clinical testing	This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 93 of the NF1 protein (p.Cys93Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with neurofibromatosis type 1 (PMID: 10862084; Invitae). ClinVar contains an entry for this variant (Variation ID: 68328). 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 variant disrupts the p.Cys93 amino acid residue in NF1. Other variant(s) that disrupt this residue have been observed in individuals with NF1-related conditions (PMID: 17426081, 23668869), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000466535	SCV000781870	pathogenic	Neurofibromatosis, type 1	2016-11-01	criteria provided, single submitter	clinical testing
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	RCV000059180	SCV002051491	likely pathogenic	not provided	2020-11-23	criteria provided, single submitter	clinical testing	PP2, PP3, PS4_Supporting, PM5_Supporting, PM2
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000059180	SCV004026456	likely pathogenic	not provided	2021-11-03	criteria provided, single submitter	clinical testing	PP3, PM2_SUP, PM5
Baylor Genetics	RCV003460652	SCV004190782	likely pathogenic	Juvenile myelomonocytic leukemia	2022-10-29	criteria provided, single submitter	clinical testing
UniProtKB/Swiss-Prot	RCV000059180	SCV000090709	not provided	not provided		no assertion provided	not provided
Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare	RCV000466535	SCV000925777	likely pathogenic	Neurofibromatosis, type 1	2018-09-27	no assertion criteria provided	clinical testing