VCV000008662.1 - ClinVar

NM_000163.5(GHR):c.335G>C (p.Cys112Ser)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000163.5(GHR):c.335G>C (p.Cys112Ser)

Variation ID: 8662 Accession: VCV000008662.1

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 5p12 5: 42694985 (GRCh38) [ NCBI UCSC ] 5: 42695087 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jan 7, 2018	Jan 7, 2018	Jun 1, 2007

HGVS

Nucleotide	Protein	Molecular consequence
NM_000163.5:c.335G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000154.1:p.Cys112Ser	missense
NM_001242399.2:c.356G>C	NP_001229328.1:p.Cys119Ser	missense
NM_001242400.2:c.335G>C	NP_001229329.1:p.Cys112Ser	missense
NM_001242401.4:c.335G>C	NP_001229330.1:p.Cys112Ser	missense
NM_001242402.2:c.335G>C	NP_001229331.1:p.Cys112Ser	missense
NM_001242403.3:c.335G>C	NP_001229332.1:p.Cys112Ser	missense
NM_001242404.2:c.335G>C	NP_001229333.1:p.Cys112Ser	missense
NM_001242405.2:c.335G>C	NP_001229334.1:p.Cys112Ser	missense
NM_001242406.2:c.335G>C	NP_001229335.1:p.Cys112Ser	missense
NM_001242460.2:c.269G>C	NP_001229389.1:p.Cys90Ser	missense
NM_001242462.1:c.335G>C	NP_001229391.1:p.Cys112Ser	missense
NC_000005.10:g.42694985G>C
NC_000005.9:g.42695087G>C
NG_011688.2:g.276062G>C

... more HGVS ... less HGVS

Protein change

C112S, C90S, C119S

Other names

Canonical SPDI

NC_000005.10:42694984:G:C

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA119817 OMIM: 600946.0032 dbSNP: rs121909372 VarSome

Comment on variant

NCBI staff reviewed the sequence information reported in PubMed 17405847 to determine the location of this allele on current reference sequence.

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
GHR		-	-	GRCh38 GRCh37	482	525

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Laron-type isolated somatotropin defect	Pathogenic (1)	no assertion criteria provided	Jun 1, 2007	RCV000009194.4

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Jun 01, 2007)	no assertion criteria provided Method: literature only	LARON SYNDROME Affected status: not provided Allele origin: germline	OMIM Accession: SCV000029411.2 First in ClinVar: Apr 04, 2013 Last updated: Jan 07, 2018	Publications: PubMed (1) PubMed: 17405847 Comment on evidence: In 2 sisters with Laron syndrome (262500) from a nonconsanguineous Austrian family, Fang et al. (2007) identified compound heterozygosity for 2 mutations in the GHR … (more) In 2 sisters with Laron syndrome (262500) from a nonconsanguineous Austrian family, Fang et al. (2007) identified compound heterozygosity for 2 mutations in the GHR gene: a G-to-C transversion in exon 5, resulting in a cys94-to-ser (C94S) substitution, inherited from the father; and a T-to-G transversion in exon 6, resulting in a his150-to-gln (H150Q; 600946.0033) substitution, inherited from the mother. In vitro reconstitution experiments showed that whereas each of the mutants could be stably expressed, C94S lost its affinity for GH and could neither activate STAT5B (604260) nor drive STAT5B-dependent gene transcription in response to GH (1-100 ng/ml). Fang et al. (2007) concluded that each of the compound heterozygous mutations contributed additively to the GHI. Both of the mutations are located in the extracellular domain of the GHR. Functional studies suggested that the C94S heterozygous state may cause partial GHI, although the impact on growth appeared to be modest. (less)

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Primary growth hormone (GH) insensitivity and insulin-like growth factor deficiency caused by novel compound heterozygous mutations of the GH receptor gene: genetic and functional studies of simple and compound heterozygous states.	Fang P	The Journal of clinical endocrinology and metabolism	2007	PMID: 17405847

Text-mined citations for rs121909372 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Dec 30, 2023

ClinVar Genomic variation as it relates to human health

NM_000163.5(GHR):c.335G>C (p.Cys112Ser)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs121909372 ...