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NM_001379200.1(TBX1):c.1376C>T (p.Ala459Val) AND DiGeorge syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 5, 2021
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:
RCV002008145.6

Allele description [Variation Report for NM_001379200.1(TBX1):c.1376C>T (p.Ala459Val)]

NM_001379200.1(TBX1):c.1376C>T (p.Ala459Val)

Gene:
TBX1:T-box transcription factor 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
22q11.21
Genomic location:
Preferred name:
NM_001379200.1(TBX1):c.1376C>T (p.Ala459Val)
HGVS:
  • NC_000022.11:g.19766728C>T
  • NG_009229.1:g.15026C>T
  • NM_001379200.1:c.1376C>TMANE SELECT
  • NM_005992.1:c.1009+726C>T
  • NM_080646.2:c.1009+726C>T
  • NM_080647.1:c.1349C>T
  • NP_001366129.1:p.Ala459Val
  • NP_542378.1:p.Ala450Val
  • LRG_226t1:c.1349C>T
  • LRG_226:g.15026C>T
  • LRG_226p1:p.Ala450Val
  • NC_000022.10:g.19754251C>T
Protein change:
A450V
Links:
dbSNP: rs1936866904
NCBI 1000 Genomes Browser:
rs1936866904
Molecular consequence:
  • NM_005992.1:c.1009+726C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_080646.2:c.1009+726C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001379200.1:c.1376C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_080647.1:c.1349C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
DiGeorge syndrome
Synonyms:
Hypoplasia of thymus and parathyroid; Third and fourth pharyngeal pouch syndrome; DiGeorge anomaly; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008564; MedGen: C0012236; Orphanet: 567; OMIM: 188400

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002262061Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Apr 5, 2021) 		germlineclinical testing

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

Help

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002262061.3

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

Description

This variant is not present in population databases (ExAC no frequency). 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. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with TBX1-related conditions. This sequence change replaces alanine with valine at codon 450 of the TBX1 protein (p.Ala450Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine.

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

Last Updated: Sep 29, 2024