NM_000515.5(GH1):c.413A>G (p.Asp138Gly) AND Short stature due to growth hormone qualitative anomaly

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 1, 1997
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:: RCV000017344.29

Allele description [Variation Report for NM_000515.5(GH1):c.413A>G (p.Asp138Gly)]

NM_000515.5(GH1):c.413A>G (p.Asp138Gly)

Genes:

GH1:growth hormone 1 [Gene - OMIM - HGNC]
GH-LCR:growth hormone locus control region [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

17q23.3

Genomic location:

Preferred name:

NM_000515.5(GH1):c.413A>G (p.Asp138Gly)

Other names:

D112G

HGVS:

NC_000017.11:g.63917803T>C
NG_011676.1:g.6036A>G
NG_042788.1:g.711T>C
NM_000515.5:c.413A>GMANE SELECT
NM_022559.4:c.368A>G
NM_022560.4:c.293A>G
NP_000506.2:p.Asp138Gly
NP_072053.1:p.Asp123Gly
NP_072054.1:p.Asp98Gly
NC_000017.10:g.61995163T>C
P01241:p.Asp138Gly

Protein change:

D123G; ASP112GLY

Links:

UniProtKB: P01241#VAR_015813; OMIM: 139250.0013; dbSNP: rs137853221

NCBI 1000 Genomes Browser:

rs137853221

Molecular consequence:

NM_000515.5:c.413A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_022559.4:c.368A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_022560.4:c.293A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Short stature due to growth hormone qualitative anomaly
Synonyms:: Kowarski syndrome; Biodefective growth hormone; Pituitary dwarfism with normal immunoreactive growth hormone and low somatomedin
Identifiers:: MONDO: MONDO:0009879; MedGen: C1849779; OMIM: 262650

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000037616	OMIM	no assertion criteria provided	Pathogenic (Sep 1, 1997)	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

SCV000037616

OMIM

no assertion criteria provided

Pathogenic
(Sep 1, 1997)

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

Biologically inactive growth hormone caused by an amino acid substitution.

Takahashi Y, Shirono H, Arisaka O, Takahashi K, Yagi T, Koga J, Kaji H, Okimura Y, Abe H, Tanaka T, Chihara K.

J Clin Invest. 1997 Sep 1;100(5):1159-65.

PubMed [citation]

PMID:: 9276733
PMCID:: PMC508291

Details of each submission

From OMIM, SCV000037616.3

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

Description

In a child presenting with short stature, Takahashi et al. (1997) demonstrated a biologically inactive growth hormone (see Kowarski syndrome, 262650) resulting from a heterozygous single-base substitution (A to G) in exon 4 of the GH1 gene. This change resulted in an asp112-to-gly (D112G) amino acid substitution. At age 3 years, the girl's height was 3.6 standard deviations below the mean for age and sex. Bone age was delayed by 1.5 years. She had a prominent forehead and a hypoplastic nasal bridge with normal body proportions. She showed lack of growth hormone action despite high immunoassayable GH levels in serum and marked catch-up growth to exogenous GH administration. Results of other studies were compatible with the production of a bioinactive GH, which prevented dimerization of the growth hormone receptor, a crucial step in GH signal transduction.

#	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: Apr 23, 2022

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