NM_000267.3(NF1):c.4310A>G (p.Glu1437Gly) AND Neurofibromatosis, type 1

Clinical significance:Likely pathogenic (Last evaluated: Apr 13, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000231680.4

Allele description [Variation Report for NM_000267.3(NF1):c.4310A>G (p.Glu1437Gly)]

NM_000267.3(NF1):c.4310A>G (p.Glu1437Gly)

Gene:
NF1:neurofibromin 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q11.2
Genomic location:
Preferred name:
NM_000267.3(NF1):c.4310A>G (p.Glu1437Gly)
HGVS:
  • NC_000017.11:g.31259072A>G
  • NG_009018.1:g.169096A>G
  • NM_000267.3:c.4310A>G
  • NM_001042492.2:c.4373A>G
  • NP_000258.1:p.Glu1437Gly
  • NP_001035957.1:p.Glu1458Gly
  • LRG_214t1:c.4310A>G
  • LRG_214t2:c.4373A>G
  • LRG_214:g.169096A>G
  • LRG_214p1:p.Glu1437Gly
  • LRG_214p2:p.Glu1458Gly
  • NC_000017.10:g.29586090A>G
Protein change:
E1437G
Links:
dbSNP: rs878853894
NCBI 1000 Genomes Browser:
rs878853894
Molecular consequence:
  • NM_000267.3:c.4310A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001042492.2:c.4373A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000284459Invitaecriteria provided, single submitter
Likely pathogenic
(Apr 13, 2016)
germlineclinical testing

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

SCV000692354Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospitalno assertion criteria providedUncertain significance
(Apr 1, 2016)
germlineclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000284459.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces glutamic acid with glycine at codon 1437 of the NF1 protein (p.Glu1437Gly). The glutamic acid residue is moderately conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with neurofibromatosis type 1 in the Leiden Open-source Variation Database (PMID: 21520333, 23656349). It has also been observed as a de novo variant in an individual with suspected neurofibromatosis type 1 (Invitae database). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, this is a rare variant with uncertain impact on protein function that has only been reported in affected individuals. However, in the absence of additional genetic and/or functional data, this variant has been classified as Likely Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital, SCV000692354.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 17, 2020

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