NM_000516.7(GNAS):c.1173C>R (p.Tyr391Ter) AND Pseudohypoparathyroidism type 1C

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 1, 2002
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:
RCV000017329.29

Allele description [Variation Report for NM_000516.7(GNAS):c.1173C>R (p.Tyr391Ter)]

NM_000516.7(GNAS):c.1173C>R (p.Tyr391Ter)

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.1173C>R (p.Tyr391Ter)
Other names:
Y391*
HGVS:
  • NC_000020.11:g.58910817C>R
  • NG_016194.2:g.76078C>R
  • NM_000516.7:c.1173C>RMANE SELECT
  • NM_001077488.5:c.1176C>R
  • NM_001077489.4:c.1128C>R
  • NM_001077490.3:c.*1034C>R
  • NM_001309840.2:c.996C>R
  • NM_001309861.2:c.996C>R
  • NM_016592.5:c.*1079C>R
  • NM_080425.4:c.3102C>R
  • NM_080426.4:c.1131C>R
  • NP_000507.1:p.Tyr391Ter
  • NP_001070956.1:p.Tyr392Ter
  • NP_001070957.1:p.Tyr376Ter
  • NP_001296769.1:p.Tyr332Ter
  • NP_001296790.1:p.Tyr332Ter
  • NP_536350.2:p.Tyr1034Ter
  • NP_536351.1:p.Tyr377Ter
  • NC_000020.10:g.57485872C>R
Note:
NCBI staff could not provide an explicit HGVS expression for allelic variant 139320.0036 because there was not enough information to determine whether the nucleotide change was NM_001077488.5:c.1176C>G or NM_001077488.5:c.1176C>A.
Protein change:
Y1034*; TYR391TER
Links:
OMIM: 139320.0036; dbSNP: rs1254063262
NCBI 1000 Genomes Browser:
rs1254063262
Molecular consequence:
  • NM_001077490.3:c.*1034C>R - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_016592.5:c.*1079C>R - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_000516.7:c.1173C>R - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001077488.5:c.1176C>R - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001077489.4:c.1128C>R - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001309840.2:c.996C>R - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001309861.2:c.996C>R - nonsense - [Sequence Ontology: SO:0001587]
  • NM_080425.4:c.3102C>R - nonsense - [Sequence Ontology: SO:0001587]
  • NM_080426.4:c.1131C>R - 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
SCV000037601OMIM
no assertion criteria provided
Pathogenic
(Jan 1, 2002) 		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

GNAS1 lesions in pseudohypoparathyroidism Ia and Ic: genotype phenotype relationship and evidence of the maternal transmission of the hormonal resistance.

Linglart A, Carel JC, Garabédian M, Lé T, Mallet E, Kottler ML.

J Clin Endocrinol Metab. 2002 Jan;87(1):189-97.

PubMed [citation]
PMID:
11788646

Details of each submission

From OMIM, SCV000037601.3

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

Description

In a girl with PHP type Ic (612462), Linglart et al. (2002) identified a heterozygous mutation in exon 13 of the GNAS gene, resulting in a tyr319-to-ter (Y391X) substitution only 4 amino acids before the wildtype stop codon. She had hormone resistance with features of Albright hereditary osteodystrophy and decreased cAMP response to PTH infusion, but normal erythrocyte Gs activity. The findings suggested that the mutation interfered somehow with receptor-mediated activation. Linglart et al. (2002) noted that the C terminus is required for receptor coupling, and postulated that the Y391X mutation in this patient interrupted receptor coupling, leading to hormone resistance. The findings showed the limits of the erythrocyte Gs bioassay used in the study.

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

Last Updated: Dec 24, 2023