NM_002397.5(MEF2C):c.788G>T (p.Ser263Ile) AND Intellectual disability, autosomal dominant 20

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 22, 2022
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:: RCV001870118.6

Allele description [Variation Report for NM_002397.5(MEF2C):c.788G>T (p.Ser263Ile)]

NM_002397.5(MEF2C):c.788G>T (p.Ser263Ile)

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.788G>T (p.Ser263Ile)

HGVS:

NC_000005.10:g.88731751C>A
NG_023427.1:g.177355G>T
NM_001131005.2:c.782G>T
NM_001193347.1:c.842G>T
NM_001193348.1:c.644G>T
NM_001193349.3:c.644G>T
NM_001193350.2:c.788G>T
NM_001308002.3:c.788G>T
NM_001363581.2:c.788G>T
NM_001364329.2:c.788G>T
NM_001364330.2:c.788G>T
NM_001364331.2:c.788G>T
NM_001364332.2:c.644G>T
NM_001364333.2:c.788G>T
NM_001364334.2:c.788G>T
NM_001364335.2:c.788G>T
NM_001364336.2:c.788G>T
NM_001364337.2:c.788G>T
NM_001364338.2:c.842G>T
NM_001364339.2:c.788G>T
NM_001364340.2:c.788G>T
NM_001364341.2:c.788G>T
NM_001364342.2:c.788G>T
NM_001364343.2:c.782G>T
NM_001364344.2:c.644G>T
NM_001364345.2:c.788G>T
NM_001364346.2:c.788G>T
NM_001364347.2:c.788G>T
NM_001364348.2:c.788G>T
NM_001364349.2:c.788G>T
NM_001364350.2:c.788G>T
NM_001364352.2:c.782G>T
NM_001364353.2:c.410G>T
NM_001364354.2:c.644G>T
NM_001364355.2:c.644G>T
NM_001364356.2:c.410G>T
NM_001364357.2:c.362G>T
NM_002397.5:c.788G>TMANE SELECT
NP_001124477.1:p.Ser261Ile
NP_001180276.1:p.Ser281Ile
NP_001180277.1:p.Ser215Ile
NP_001180278.1:p.Ser215Ile
NP_001180279.1:p.Ser263Ile
NP_001294931.1:p.Ser263Ile
NP_001350510.1:p.Ser263Ile
NP_001351258.1:p.Ser263Ile
NP_001351259.1:p.Ser263Ile
NP_001351260.1:p.Ser263Ile
NP_001351261.1:p.Ser215Ile
NP_001351262.1:p.Ser263Ile
NP_001351263.1:p.Ser263Ile
NP_001351264.1:p.Ser263Ile
NP_001351265.1:p.Ser263Ile
NP_001351266.1:p.Ser263Ile
NP_001351267.1:p.Ser281Ile
NP_001351268.1:p.Ser263Ile
NP_001351269.1:p.Ser263Ile
NP_001351270.1:p.Ser263Ile
NP_001351271.1:p.Ser263Ile
NP_001351272.1:p.Ser261Ile
NP_001351273.1:p.Ser215Ile
NP_001351274.1:p.Ser263Ile
NP_001351275.1:p.Ser263Ile
NP_001351276.1:p.Ser263Ile
NP_001351277.1:p.Ser263Ile
NP_001351278.1:p.Ser263Ile
NP_001351279.1:p.Ser263Ile
NP_001351281.1:p.Ser261Ile
NP_001351282.1:p.Ser137Ile
NP_001351283.1:p.Ser215Ile
NP_001351284.1:p.Ser215Ile
NP_001351285.1:p.Ser137Ile
NP_001351286.1:p.Ser121Ile
NP_002388.2:p.Ser263Ile
NC_000005.9:g.88027568C>A

Protein change:

S121I

Links:

dbSNP: rs2152279598

NCBI 1000 Genomes Browser:

rs2152279598

Molecular consequence:

NM_001131005.2:c.782G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001193347.1:c.842G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001193348.1:c.644G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001193349.3:c.644G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001193350.2:c.788G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001308002.3:c.788G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363581.2:c.788G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364329.2:c.788G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364330.2:c.788G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364331.2:c.788G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364332.2:c.644G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364333.2:c.788G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364334.2:c.788G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364335.2:c.788G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364336.2:c.788G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364337.2:c.788G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364338.2:c.842G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364339.2:c.788G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364340.2:c.788G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364341.2:c.788G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364342.2:c.788G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364343.2:c.782G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364344.2:c.644G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364345.2:c.788G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364346.2:c.788G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364347.2:c.788G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364348.2:c.788G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364349.2:c.788G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364350.2:c.788G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364352.2:c.782G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364353.2:c.410G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364354.2:c.644G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364355.2:c.644G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364356.2:c.410G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001364357.2:c.362G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002397.5:c.788G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Intellectual disability, autosomal dominant 20 (NEDHSIL)
Synonyms:: NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA, STEREOTYPIC HAND MOVEMENTS, AND IMPAIRED LANGUAGE
Identifiers:: MONDO: MONDO:0013266; MedGen: C3150700; Orphanet: 228384; OMIM: 613443

Recent activity

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Homo sapiens R3H domain and coiled-coil containing 1, mRNA (cDNA clone IMAGE:522...
Homo sapiens R3H domain and coiled-coil containing 1, mRNA (cDNA clone IMAGE:5220614)
gi|22749792|gb|BC032421.1|

Nucleotide
PREDICTED: Mus musculus tetratricopeptide repeat domain 29 (Ttc29), transcript v...
PREDICTED: Mus musculus tetratricopeptide repeat domain 29 (Ttc29), transcript variant X4, mRNA
gi|1039790822|ref|XM_011248517.2|

Nucleotide
PREDICTED: Mus musculus cancer susceptibility candidate 1 (Casc1), transcript va...
PREDICTED: Mus musculus cancer susceptibility candidate 1 (Casc1), transcript variant X14, mRNA
gi|1039775298|ref|XM_017321645.1|

Nucleotide
PREDICTED: probable receptor-like protein kinase At1g80640 [Cucumis melo]
PREDICTED: probable receptor-like protein kinase At1g80640 [Cucumis melo]
gi|659088958|ref|XP_008445251.1|

Protein
protein GLUTAMINE DUMPER 5 [Cucumis sativus]
protein GLUTAMINE DUMPER 5 [Cucumis sativus]
gi|778696825|ref|XP_004151217.2|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002118915	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 22, 2022)	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

SCV002118915

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 22, 2022)

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, SCV002118915.3

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

Description

This variant has not been reported in the literature in individuals affected with MEF2C-related conditions. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MEF2C protein function. ClinVar contains an entry for this variant (Variation ID: 1356476). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 263 of the MEF2C protein (p.Ser263Ile).

#	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

ClinVar

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