NM_001042492.3(NF1):c.7181T>A (p.Leu2394His) AND Neurofibromatosis, type 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 13, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001910003.6

Allele description [Variation Report for NM_001042492.3(NF1):c.7181T>A (p.Leu2394His)]

NM_001042492.3(NF1):c.7181T>A (p.Leu2394His)

Gene:

NF1:neurofibromin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q11.2

Genomic location:

Preferred name:

NM_001042492.3(NF1):c.7181T>A (p.Leu2394His)

HGVS:

NC_000017.11:g.31343127T>A
NG_009018.1:g.253151T>A
NM_000267.3:c.7118T>A
NM_001042492.3:c.7181T>AMANE SELECT
NP_000258.1:p.Leu2373His
NP_001035957.1:p.Leu2394His
LRG_214t1:c.7118T>A
LRG_214:g.253151T>A
LRG_214p1:p.Leu2373His
NC_000017.10:g.29670145T>A

Protein change:

L2373H

Links:

dbSNP: rs1135402899

NCBI 1000 Genomes Browser:

rs1135402899

Molecular consequence:

NM_000267.3:c.7118T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001042492.3:c.7181T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Neurofibromatosis, type 1 (NF1)
Synonyms:: NEUROFIBROMATOSIS, TYPE I; Recklinghausen's disease; Von Recklinghausen disease; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0018975; MedGen: C0027831; Orphanet: 636; OMIM: 162200

Recent activity

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SRX2033537 (1)
SRA
protein ALP1-like [Cucurbita maxima]
protein ALP1-like [Cucurbita maxima]
gi|1281045448|ref|XP_023007481.1|

Protein
mucin-13 [Rattus norvegicus]
mucin-13 [Rattus norvegicus]
gi|2505756809|ref|NP_001408226.1|

Protein
RING finger and CHY zinc finger domain-containing protein 1 isoform 1 [Homo sapi...
RING finger and CHY zinc finger domain-containing protein 1 isoform 1 [Homo sapiens]
gi|58331195|ref|NP_056251.2|

Protein
Chain C, Cell division protein kinase 4
Chain C, Cell division protein kinase 4
gi|224983655|pdb|3G33|C

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002182593	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 13, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002182593

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 13, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002182593.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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. This variant has not been reported in the literature in individuals with NF1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with histidine at codon 2373 of the NF1 protein (p.Leu2373His). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and histidine.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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