NM_003466.4(PAX8):c.170G>A (p.Cys57Tyr) AND Hypothyroidism, congenital, nongoitrous, 2

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 1, 2001
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV000014796.27

Allele description [Variation Report for NM_003466.4(PAX8):c.170G>A (p.Cys57Tyr)]

NM_003466.4(PAX8):c.170G>A (p.Cys57Tyr)

Genes:
PAX8-AS1:PAX8 antisense RNA 1 [Gene - HGNC]
PAX8:paired box 8 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q14.1
Genomic location:
Preferred name:
NM_003466.4(PAX8):c.170G>A (p.Cys57Tyr)
HGVS:
  • NC_000002.12:g.113246775C>T
  • NG_012384.1:g.37147G>A
  • NM_003466.4:c.170G>AMANE SELECT
  • NM_013952.4:c.170G>A
  • NM_013953.4:c.170G>A
  • NM_013992.4:c.170G>A
  • NP_003457.1:p.Cys57Tyr
  • NP_039246.1:p.Cys57Tyr
  • NP_039247.1:p.Cys57Tyr
  • NP_054698.1:p.Cys57Tyr
  • NC_000002.11:g.114004352C>T
  • Q06710:p.Cys57Tyr
Protein change:
C57Y; CYS57TYR
Links:
UniProtKB: Q06710#VAR_012771; OMIM: 167415.0005; dbSNP: rs104893659
NCBI 1000 Genomes Browser:
rs104893659
Molecular consequence:
  • NM_003466.4:c.170G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_013952.4:c.170G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_013953.4:c.170G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_013992.4:c.170G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hypothyroidism, congenital, nongoitrous, 2 (CHNG2)
Synonyms:
Hypothyroidism, congenital, due to thyroid dysgenesis or hypoplasia
Identifiers:
MONDO: MONDO:0024264; MedGen: C1869118; Orphanet: 95712; OMIM: 218700

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
SCV000035051OMIM
no assertion criteria provided
Pathogenic
(Jan 1, 2001) 		germlineliterature only

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Autosomal dominant transmission of congenital thyroid hypoplasia due to loss-of-function mutation of PAX8.

Vilain C, Rydlewski C, Duprez L, Heinrichs C, Abramowicz M, Malvaux P, Renneboog B, Parma J, Costagliola S, Vassart G.

J Clin Endocrinol Metab. 2001 Jan;86(1):234-8.

PubMed [citation]
PMID:
11232006

Details of each submission

From OMIM, SCV000035051.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In a mother and daughter with congenital hypothyroidism (CHNG2; 218700) and aplasia and hypoplasia of the thyroid gland, respectively, Vilain et al. (2001) identified heterozygosity for a G-A transition in exon 3 of the PAX8 gene, resulting in a cys57-to-tyr (C57Y) substitution in the paired domain of the protein. An unaffected second daughter in the family did not carry the mutation. When tested in cotransfection experiments with a thyroid peroxidase promoter construct, the mutant allele was unable to exert its normal transactivation effect on transcription. The authors concluded that, contrary to the situation in knockout mice, haploinsufficiency of PAX8 is a cause of congenital hypothyroidism in humans.

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

Last Updated: May 24, 2022