Submissions for variant NM_001042492.3(NF1):c.1185G>A (p.Lys395=)

dbSNP: rs1567835847

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000705299	SCV000834289	pathogenic	Neurofibromatosis, type 1	2024-09-12	criteria provided, single submitter	clinical testing	This sequence change affects codon 395 of the NF1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the NF1 protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with clinically features of neurofibromatosis type 1 (PMID: 22034633, 24789688; internal data). This variant is also known as the last nucleotide of exon 8. ClinVar contains an entry for this variant (Variation ID: 581467). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of 10, but is expected to preserve the integrity of the reading-frame (PMID: 24789688). For these reasons, this variant has been classified as Pathogenic.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV000705299	SCV001479054	likely pathogenic	Neurofibromatosis, type 1	2020-10-26	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000705299	SCV002561635	likely pathogenic	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing