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NM_000516.7(GNAS):c.1174G>T (p.Glu392Ter) AND Pseudohypoparathyroidism type 1C

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 1, 2011
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:
RCV000022597.28

Allele description [Variation Report for NM_000516.7(GNAS):c.1174G>T (p.Glu392Ter)]

NM_000516.7(GNAS):c.1174G>T (p.Glu392Ter)

Gene:
GNAS:GNAS complex locus [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
20q13.32
Genomic location:
Preferred name:
NM_000516.7(GNAS):c.1174G>T (p.Glu392Ter)
HGVS:
  • NC_000020.11:g.58910818G>T
  • NG_016194.2:g.76079G>T
  • NM_000516.7:c.1174G>TMANE SELECT
  • NM_001077488.5:c.1177G>T
  • NM_001077489.4:c.1129G>T
  • NM_001077490.3:c.*1035G>T
  • NM_001309840.2:c.997G>T
  • NM_001309861.2:c.997G>T
  • NM_016592.5:c.*1080G>T
  • NM_080425.4:c.3103G>T
  • NM_080426.4:c.1132G>T
  • NP_000507.1:p.Glu392Ter
  • NP_001070956.1:p.Glu393Ter
  • NP_001070957.1:p.Glu377Ter
  • NP_001296769.1:p.Glu333Ter
  • NP_001296790.1:p.Glu333Ter
  • NP_536350.2:p.Glu1035Ter
  • NP_536351.1:p.Glu378Ter
  • NC_000020.10:g.57485873G>T
Protein change:
E1035*; GLU392TER
Links:
OMIM: 139320.0039; dbSNP: rs397514456
NCBI 1000 Genomes Browser:
rs397514456
Molecular consequence:
  • NM_001077490.3:c.*1035G>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_016592.5:c.*1080G>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000516.7:c.1174G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001077488.5:c.1177G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001077489.4:c.1129G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001309840.2:c.997G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001309861.2:c.997G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_080425.4:c.3103G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_080426.4:c.1132G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Pseudohypoparathyroidism type 1C (PHP1C)
Synonyms:
PSEUDOHYPOPARATHYROIDISM, TYPE IC; PHP IC
Identifiers:
MONDO: MONDO:0012911; MedGen: C2932716; Orphanet: 79444; OMIM: 612462

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000043886OMIM
no assertion criteria provided
Pathogenic
(Jun 1, 2011) 		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

Functional characterization of GNAS mutations found in patients with pseudohypoparathyroidism type Ic defines a new subgroup of pseudohypoparathyroidism affecting selectively Gsα-receptor interaction.

Thiele S, de Sanctis L, Werner R, Grötzinger J, Aydin C, Jüppner H, Bastepe M, Hiort O.

Hum Mutat. 2011 Jun;32(6):653-60. doi: 10.1002/humu.21489. Epub 2011 Apr 12.

PubMed [citation]
PMID:
21488135
PMCID:
PMC3103608

Details of each submission

From OMIM, SCV000043886.2

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

Description

In 13-year-old dizygotic twins and an unrelated 5-year-old girl with PHP IC (612462), Thiele et al. (2011) identified a heterozygous 1174G-T transversion in exon 13 of the GNAS gene, resulting in a glu392-to-ter (E392X) substitution in the alpha-5-helix in the C terminus. The patients had characteristic features of AHO, including round face, brachymetacarpia, short stature, and obesity. Serum PTH and TSH were increased and calcium was low. Both mothers, who also carried the mutation, had short stature, round face, and/or brachymetacarpia, but no evidence of hormone resistance. In vitro functional expression studies showed that the mutant protein caused complete absence of receptor-mediated cAMP production, with normal receptor-independent cAMP production. The findings indicated normal Gs-alpha activity, but a selective defect in Gs-alpha-receptor coupling functions.

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

Last Updated: Sep 17, 2022