NM_000268.4(NF2):c.1303G>T (p.Val435Leu) AND Neurofibromatosis, type 2

Clinical significance:Uncertain significance (Last evaluated: Jan 31, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000525241.1

Allele description [Variation Report for NM_000268.4(NF2):c.1303G>T (p.Val435Leu)]

NM_000268.4(NF2):c.1303G>T (p.Val435Leu)

Gene:
NF2:NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
22q12.2
Genomic location:
Preferred name:
NM_000268.4(NF2):c.1303G>T (p.Val435Leu)
HGVS:
  • NC_000022.11:g.29673449G>T
  • NG_009057.1:g.74894G>T
  • NM_000268.4:c.1303G>TMANE SELECT
  • NM_016418.5:c.1303G>T
  • NM_181825.3:c.1303G>T
  • NM_181828.3:c.1177G>T
  • NM_181829.3:c.1180G>T
  • NM_181830.3:c.1054G>T
  • NM_181831.3:c.1054G>T
  • NM_181832.3:c.1303G>T
  • NM_181833.3:c.448-21303G>T
  • NP_000259.1:p.Val435Leu
  • NP_000259.1:p.Val435Leu
  • NP_057502.2:p.Val435Leu
  • NP_861546.1:p.Val435Leu
  • NP_861966.1:p.Val393Leu
  • NP_861967.1:p.Val394Leu
  • NP_861968.1:p.Val352Leu
  • NP_861969.1:p.Val352Leu
  • NP_861970.1:p.Val435Leu
  • LRG_511t1:c.1303G>T
  • LRG_511t2:c.1303G>T
  • LRG_511:g.74894G>T
  • LRG_511p1:p.Val435Leu
  • LRG_511p2:p.Val435Leu
  • NC_000022.10:g.30069438G>T
  • NM_000268.3:c.1303G>T
  • NR_156186.2:n.1785G>T
Protein change:
V352L
Links:
dbSNP: rs772334382
NCBI 1000 Genomes Browser:
rs772334382
Molecular consequence:
  • NM_181833.3:c.448-21303G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000268.4:c.1303G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_016418.5:c.1303G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181825.3:c.1303G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181828.3:c.1177G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181829.3:c.1180G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181830.3:c.1054G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181831.3:c.1054G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181832.3:c.1303G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_156186.2:n.1785G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Neurofibromatosis, type 2 (NF2)
Synonyms:
NF 2; Neurofibromatosis central type; Acoustic schwannomas bilateral; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007039; MedGen: C0027832; Orphanet: 637; OMIM: 101000

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000628847Invitaecriteria provided, single submitter
Uncertain significance
(Jan 31, 2017)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
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, SCV000628847.1

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

Description

This sequence change replaces valine with leucine at codon 435 of the NF2 protein (p.Val435Leu). The valine residue is weakly conserved and there is a small physicochemical difference between valine and leucine. This variant is present in population databases (rs772334382, ExAC 0.03%) but has not been reported in the literature in individuals with a NF2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Dec 4, 2021

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