NM_000516.7(GNAS):c.1163T>G (p.Leu388Arg) 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:: RCV000022598.28

Allele description [Variation Report for NM_000516.7(GNAS):c.1163T>G (p.Leu388Arg)]

NM_000516.7(GNAS):c.1163T>G (p.Leu388Arg)

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.1163T>G (p.Leu388Arg)

HGVS:

NC_000020.11:g.58910807T>G
NG_016194.2:g.76068T>G
NM_000516.7:c.1163T>GMANE SELECT
NM_001077488.5:c.1166T>G
NM_001077489.4:c.1118T>G
NM_001077490.3:c.*1024T>G
NM_001309840.2:c.986T>G
NM_001309861.2:c.986T>G
NM_016592.5:c.*1069T>G
NM_080425.4:c.3092T>G
NM_080426.4:c.1121T>G
NP_000507.1:p.Leu388Arg
NP_001070956.1:p.Leu389Arg
NP_001070957.1:p.Leu373Arg
NP_001296769.1:p.Leu329Arg
NP_001296790.1:p.Leu329Arg
NP_536350.2:p.Leu1031Arg
NP_536351.1:p.Leu374Arg
NC_000020.10:g.57485862T>G

Protein change:

L1031R; LEU388ARG

Links:

OMIM: 139320.0038; dbSNP: rs397514457

NCBI 1000 Genomes Browser:

rs397514457

Molecular consequence:

NM_001077490.3:c.*1024T>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_016592.5:c.*1069T>G - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_000516.7:c.1163T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001077488.5:c.1166T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001077489.4:c.1118T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001309840.2:c.986T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001309861.2:c.986T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_080425.4:c.3092T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_080426.4:c.1121T>G - missense variant - [Sequence Ontology: SO:0001583]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000043887	OMIM	no assertion criteria provided	Pathogenic (Jun 1, 2011)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000043887

OMIM

no assertion criteria provided

Pathogenic
(Jun 1, 2011)

germline

literature only

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature 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, SCV000043887.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a 12-year-old boy with PHP IC (612462), Thiele et al. (2011) identified a heterozygous 1163T-G transversion in exon 13 of the GNAS gene, resulting in a leu388-to-arg (L388R) substitution in a conserved residue in the alpha-5-helix in the C-terminal part of the protein directly involved in the contact of Gs-alpha to the G protein-coupled receptor. The patient had characteristic features of AHO, including round face, brachymetacarpia, short stature, obesity, and mental retardation. Serum PTH and TSH were increased and calcium was low. His mother, who also carried the mutation, had short stature and brachymetacarpia, but no evidence of hormone resistance. In vitro functional expression studies showed that the L388R 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 17, 2022

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