Submissions for variant NM_001042492.3(NF1):c.3732T>A (p.Val1244=)

gnomAD frequency: 0.00001  dbSNP: rs756653022

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000166431	SCV000217226	likely benign	Hereditary cancer-predisposing syndrome	2014-10-17	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000217704	SCV000270619	likely benign	not specified	2016-01-05	criteria provided, single submitter	clinical testing	p.Val1244Val variant in NF1 has been identified in 4/66738 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org/, dbSN P rs756653022). While the variant does not alter an amino acid residue, computat ional tools suggest the creation of a novel splice site. However, this informati on is not predictive enough to determine pathogenicity. Although a role in disea se cannot be fully excluded, its presence in the general population and lack of impact to the protein sequence suggests that it is likely to be benign.
Invitae	RCV000229456	SCV000284444	likely benign	Neurofibromatosis, type 1	2023-12-12	criteria provided, single submitter	clinical testing
GeneDx	RCV000217704	SCV000726806	likely benign	not specified	2018-01-11	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Sema4, Sema4	RCV000166431	SCV002527532	uncertain significance	Hereditary cancer-predisposing syndrome	2022-03-08	criteria provided, single submitter	curation
PreventionGenetics, part of Exact Sciences	RCV003965212	SCV004785515	likely benign	NF1-related condition	2022-12-10	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).