NM_000268.4(NF2):c.1018G>T (p.Ala340Ser) AND Neurofibromatosis, type 2

Clinical significance:Uncertain significance (Last evaluated: May 26, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_000268.4(NF2):c.1018G>T (p.Ala340Ser)]

NM_000268.4(NF2):c.1018G>T (p.Ala340Ser)

NF2:NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000268.4(NF2):c.1018G>T (p.Ala340Ser)
  • NC_000022.11:g.29671844G>T
  • NG_009057.1:g.73289G>T
  • NM_000268.3:c.1018G>T
  • NM_000268.4:c.1018G>TMANE SELECT
  • NM_016418.5:c.1018G>T
  • NM_181825.3:c.1018G>T
  • NM_181828.3:c.892G>T
  • NM_181829.3:c.895G>T
  • NM_181830.3:c.769G>T
  • NM_181831.3:c.769G>T
  • NM_181832.3:c.1018G>T
  • NM_181833.3:c.448-22908G>T
  • NP_000259.1:p.Ala340Ser
  • NP_000259.1:p.Ala340Ser
  • NP_057502.2:p.Ala340Ser
  • NP_861546.1:p.Ala340Ser
  • NP_861966.1:p.Ala298Ser
  • NP_861967.1:p.Ala299Ser
  • NP_861968.1:p.Ala257Ser
  • NP_861969.1:p.Ala257Ser
  • NP_861970.1:p.Ala340Ser
  • LRG_511t1:c.1018G>T
  • LRG_511t2:c.1018G>T
  • LRG_511:g.73289G>T
  • LRG_511p1:p.Ala340Ser
  • LRG_511p2:p.Ala340Ser
  • NC_000022.10:g.30067833G>T
  • NR_156186.2:n.1500G>T
Protein change:
dbSNP: rs780430071
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_181833.3:c.448-22908G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000268.3:c.1018G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000268.4:c.1018G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_016418.5:c.1018G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181825.3:c.1018G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181828.3:c.892G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181829.3:c.895G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181830.3:c.769G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181831.3:c.769G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_181832.3:c.1018G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_156186.2:n.1500G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]


Neurofibromatosis, type 2 (NF2)
NF 2; Neurofibromatosis central type; Acoustic schwannomas bilateral; See all synonyms [MedGen]
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)
SCV000553686Invitaecriteria provided, single submitter
Uncertain significance
(May 26, 2016)
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



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]

Details of each submission

From Invitae, SCV000553686.2

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


This sequence change replaces alanine with serine at codon 340 of the NF2 protein (p.Ala340Ser). The alanine residue is moderately conserved and there is a moderate physicochemical difference between alanine and serine. This variant is not present in population databases (ExAC no frequency) and 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 novel 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.

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

Last Updated: Oct 24, 2021

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