NM_002397.5(MEF2C):c.170A>G (p.Tyr57Cys) AND Mental retardation, stereotypic movements, epilepsy, and/or cerebral malformations

Clinical significance:Likely pathogenic (Last evaluated: May 22, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001376765.1

Allele description [Variation Report for NM_002397.5(MEF2C):c.170A>G (p.Tyr57Cys)]

NM_002397.5(MEF2C):c.170A>G (p.Tyr57Cys)

Gene:
MEF2C:myocyte enhancer factor 2C [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q14.3
Genomic location:
Preferred name:
NM_002397.5(MEF2C):c.170A>G (p.Tyr57Cys)
HGVS:
  • NC_000005.10:g.88804686T>C
  • NG_023427.1:g.104420A>G
  • NM_001131005.2:c.170A>G
  • NM_001193347.1:c.170A>G
  • NM_001193348.1:c.170A>G
  • NM_001193349.3:c.170A>G
  • NM_001193350.2:c.170A>G
  • NM_001308002.3:c.170A>G
  • NM_001363581.2:c.170A>G
  • NM_001364329.2:c.170A>G
  • NM_001364330.2:c.170A>G
  • NM_001364331.2:c.170A>G
  • NM_001364332.2:c.170A>G
  • NM_001364333.2:c.170A>G
  • NM_001364334.2:c.170A>G
  • NM_001364335.2:c.170A>G
  • NM_001364336.2:c.170A>G
  • NM_001364337.2:c.170A>G
  • NM_001364338.2:c.170A>G
  • NM_001364339.2:c.170A>G
  • NM_001364340.2:c.170A>G
  • NM_001364341.2:c.170A>G
  • NM_001364342.2:c.170A>G
  • NM_001364343.2:c.170A>G
  • NM_001364344.2:c.170A>G
  • NM_001364345.2:c.170A>G
  • NM_001364346.2:c.170A>G
  • NM_001364347.2:c.170A>G
  • NM_001364348.2:c.170A>G
  • NM_001364349.2:c.170A>G
  • NM_001364350.2:c.170A>G
  • NM_001364352.2:c.170A>G
  • NM_001364354.2:c.170A>G
  • NM_001364355.2:c.170A>G
  • NM_002397.5:c.170A>GMANE SELECT
  • NP_001124477.1:p.Tyr57Cys
  • NP_001180276.1:p.Tyr57Cys
  • NP_001180277.1:p.Tyr57Cys
  • NP_001180278.1:p.Tyr57Cys
  • NP_001180279.1:p.Tyr57Cys
  • NP_001294931.1:p.Tyr57Cys
  • NP_001350510.1:p.Tyr57Cys
  • NP_001351258.1:p.Tyr57Cys
  • NP_001351259.1:p.Tyr57Cys
  • NP_001351260.1:p.Tyr57Cys
  • NP_001351261.1:p.Tyr57Cys
  • NP_001351262.1:p.Tyr57Cys
  • NP_001351263.1:p.Tyr57Cys
  • NP_001351264.1:p.Tyr57Cys
  • NP_001351265.1:p.Tyr57Cys
  • NP_001351266.1:p.Tyr57Cys
  • NP_001351267.1:p.Tyr57Cys
  • NP_001351268.1:p.Tyr57Cys
  • NP_001351269.1:p.Tyr57Cys
  • NP_001351270.1:p.Tyr57Cys
  • NP_001351271.1:p.Tyr57Cys
  • NP_001351272.1:p.Tyr57Cys
  • NP_001351273.1:p.Tyr57Cys
  • NP_001351274.1:p.Tyr57Cys
  • NP_001351275.1:p.Tyr57Cys
  • NP_001351276.1:p.Tyr57Cys
  • NP_001351277.1:p.Tyr57Cys
  • NP_001351278.1:p.Tyr57Cys
  • NP_001351279.1:p.Tyr57Cys
  • NP_001351281.1:p.Tyr57Cys
  • NP_001351283.1:p.Tyr57Cys
  • NP_001351284.1:p.Tyr57Cys
  • NP_002388.2:p.Tyr57Cys
  • NC_000005.9:g.88100503T>C
Protein change:
Y57C
Molecular consequence:
  • NM_001131005.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001193347.1:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001193348.1:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001193349.3:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001193350.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001308002.3:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001363581.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364329.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364330.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364331.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364332.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364333.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364334.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364335.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364336.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364337.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364338.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364339.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364340.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364341.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364342.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364343.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364344.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364345.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364346.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364347.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364348.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364349.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364350.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364352.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364354.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001364355.2:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002397.5:c.170A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Mental retardation, stereotypic movements, epilepsy, and/or cerebral malformations (NEDHSIL)
Synonyms:
MENTAL RETARDATION, AUTOSOMAL DOMINANT 20; NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA, STEREOTYPIC HAND MOVEMENTS, AND IMPAIRED LANGUAGE
Identifiers:
MONDO: MONDO:0013266; MedGen: C3150700; Orphanet: 228384; OMIM: 613443

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001573929Invitaecriteria provided, single submitter
Likely pathogenic
(May 22, 2020)
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, SCV001573929.1

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

Description

This sequence change replaces tyrosine with cysteine at codon 57 of the MEF2C protein (p.Tyr57Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with MEF2C-related conditions (Invitae). In at least one individual the variant was observed to be de novo. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Sep 23, 2021

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