Submissions for variant NM_001042492.3(NF1):c.5858T>C (p.Leu1953Pro)

dbSNP: rs199474792

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000000362	SCV000935565	pathogenic	Neurofibromatosis, type 1	2023-10-18	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1932 of the NF1 protein (p.Leu1932Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with neurofibromatosis type 1 and/or NF1-related conditions (PMID: 2114220, 12522551, 31776437; Invitae). In at least one individual the variant was observed to be de novo. This variant is also known as 1045C>T. ClinVar contains an entry for this variant (Variation ID: 334). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NF1 protein function. For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV000059211	SCV002012767	uncertain significance	not provided	2019-05-07	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 12522551, 2114220, 31776437)
OMIM	RCV000000362	SCV000020506	pathogenic	Neurofibromatosis, type 1	2013-04-03	no assertion criteria provided	literature only
UniProtKB/Swiss-Prot	RCV000059211	SCV000090740	not provided	not provided		no assertion provided	not provided
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	RCV000000362	SCV004101080	pathogenic	Neurofibromatosis, type 1	2023-11-02	no assertion criteria provided	clinical testing