Submissions for variant NM_001042492.3(NF1):c.4682G>A (p.Ser1561Asn)

gnomAD frequency: 0.00001  dbSNP: rs751414513

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000199054	SCV000254502	likely benign	Neurofibromatosis, type 1	2024-12-09	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000563776	SCV000662763	uncertain significance	Hereditary cancer-predisposing syndrome	2016-01-14	criteria provided, single submitter	clinical testing	Thep.S1561Nvariant (also known as c.4682G>A)located in coding exon 35 of theNF1gene, results from a G to A substitution at nucleotide position 4682. The serine at codon 1561 is replaced by asparagine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.003% (greater than 110000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of p.S1561N remains unclear.
Mendelics	RCV000199054	SCV000839150	uncertain significance	Neurofibromatosis, type 1	2018-07-02	criteria provided, single submitter	clinical testing
GeneDx	RCV001577944	SCV001805442	likely benign	not provided	2021-02-24	criteria provided, single submitter	clinical testing	In silico analysis supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Sema4, Sema4	RCV000563776	SCV002527581	uncertain significance	Hereditary cancer-predisposing syndrome	2021-11-22	criteria provided, single submitter	curation
Ambry Genetics	RCV004558448	SCV005048218	likely benign	Hereditary cancer-predisposing syndrome; Cardiovascular phenotype	2023-03-03	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.