U.S. flag

An official website of the United States government

NM_005120.3(MED12):c.1363C>T (p.Arg455Trp) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 19, 2020
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:
RCV001819530.4

Allele description [Variation Report for NM_005120.3(MED12):c.1363C>T (p.Arg455Trp)]

NM_005120.3(MED12):c.1363C>T (p.Arg455Trp)

Genes:
LOC126863275:BRD4-independent group 4 enhancer GRCh37_chrX:70342400-70343599 [Gene]
MED12:mediator complex subunit 12 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq13.1
Genomic location:
Preferred name:
NM_005120.3(MED12):c.1363C>T (p.Arg455Trp)
HGVS:
  • NC_000023.11:g.71122752C>T
  • NG_012808.1:g.9197C>T
  • NM_005120.3:c.1363C>TMANE SELECT
  • NP_005111.2:p.Arg455Trp
  • NC_000023.10:g.70342602C>T
  • NM_005120.2:c.1363C>T
Protein change:
R455W
Links:
dbSNP: rs1268612180
NCBI 1000 Genomes Browser:
rs1268612180
Molecular consequence:
  • NM_005120.3:c.1363C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002068629Genetic Services Laboratory, University of Chicago
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Aug 19, 2020) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Genetic Services Laboratory, University of Chicago, SCV002068629.1

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

Description

DNA sequence analysis of the MED12 gene demonstrated a sequence change, c.1363C>T, in exon 10 that results in an amino acid change, p.Arg455Trp. This sequence change does not appear to have been previously described in patients with MED12-related disorders and has been described in the gnomAD database with a low population frequency of 0.0017% (dbSNP rs1268612180). The p.Arg455Trp change affects a highly conserved amino acid residue located in a domain of the MED12 protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Arg455Trp substitution. Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Arg455Trp change remains unknown at this time.

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

Last Updated: Sep 8, 2024