Submissions for variant NM_001042492.3(NF1):c.5886dup (p.Asn1963Ter)

dbSNP: rs2069603579

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001230298	SCV001402773	pathogenic	Neurofibromatosis, type 1	2023-04-19	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 957335). This variant has not been reported in the literature in individuals affected with NF1-related conditions. This sequence change creates a premature translational stop signal (p.Asn1942*) in the NF1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538).
GeneDx	RCV004800737	SCV005421198	pathogenic	not provided	2024-06-05	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease
PreventionGenetics, part of Exact Sciences	RCV004548084	SCV004765789	pathogenic	NF1-related disorder	2023-11-27	no assertion criteria provided	clinical testing	The NF1 c.5886dupT variant is predicted to result in premature protein termination (p.Asn1963*). This variant is also referred to as c.5823dup (p.Asn1942*) in an alternate transcript (NM_000267.3). To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. Nonsense variants in NF1 are expected to be pathogenic. This variant is interpreted as pathogenic.