Submissions for variant NM_001042492.3(NF1):c.2178G>C (p.Val726=)

gnomAD frequency: 0.00010  dbSNP: rs369590240

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163502	SCV000214060	likely benign	Hereditary cancer-predisposing syndrome	2014-12-09	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001083588	SCV000284404	benign	Neurofibromatosis, type 1	2025-02-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000420184	SCV000533509	likely benign	not provided	2021-10-27	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 18925961)
Illumina Laboratory Services, Illumina	RCV001127929	SCV001287289	uncertain significance	Neurofibromatosis, familial spinal	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001127930	SCV001287290	uncertain significance	Café-au-lait macules with pulmonary stenosis	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001127931	SCV001287291	uncertain significance	Neurofibromatosis-Noonan syndrome	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001083588	SCV001287292	uncertain significance	Neurofibromatosis, type 1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Genetic Services Laboratory, University of Chicago	RCV001818366	SCV002065708	benign	not specified	2021-03-19	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000163502	SCV002527450	benign	Hereditary cancer-predisposing syndrome	2020-07-14	criteria provided, single submitter	curation
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000163502	SCV005415576	likely benign	Hereditary cancer-predisposing syndrome	2024-08-12	criteria provided, single submitter	clinical testing	The p.Val726= variant is observed in 31/10,078 (0.3076%) alleles from individuals of gnomAD Ashkenazi Jewish background in gnomAD, which is greater than expected for the disorder. The p.Val726= variant is not predicted to disrupt an existing splice site. The p.Val726= variant results in a substitution of a base that is not predicted conserved by GERP++ and PhyloP. For these reasons, this variant has been classified as Likely Benign.
PreventionGenetics, part of Exact Sciences	RCV004551400	SCV004762067	likely benign	NF1-related disorder	2019-11-12	no assertion criteria provided	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).