NM_012448.4(STAT5B):c.925G>C (p.Val309Leu) AND Growth hormone insensitivity with immune dysregulation 1, autosomal recessive

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 20, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001037331.6

Allele description [Variation Report for NM_012448.4(STAT5B):c.925G>C (p.Val309Leu)]

NM_012448.4(STAT5B):c.925G>C (p.Val309Leu)

Gene:

STAT5B:signal transducer and activator of transcription 5B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.2

Genomic location:

Preferred name:

NM_012448.4(STAT5B):c.925G>C (p.Val309Leu)

HGVS:

NC_000017.11:g.42218787C>G
NG_007271.1:g.62620G>C
NM_012448.4:c.925G>CMANE SELECT
NP_036580.2:p.Val309Leu
LRG_192t1:c.925G>C
LRG_192:g.62620G>C
NC_000017.10:g.40370805C>G
NM_012448.3:c.925G>C

Protein change:

V309L

Links:

dbSNP: rs2080196988

NCBI 1000 Genomes Browser:

rs2080196988

Molecular consequence:

NM_012448.4:c.925G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Growth hormone insensitivity with immune dysregulation 1, autosomal recessive
Synonyms:: Growth hormone insensitivity with immunodeficiency; Growth hormone insensitivity due to postreceptor defect; Laron syndrome due to postreceptor defect; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0100211; MedGen: C5435698; Orphanet: 220465; OMIM: 245590

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001200741	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 20, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001200741

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 20, 2019)

germline

clinical testing

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001200741.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces valine with leucine at codon 309 of the STAT5B protein (p.Val309Leu). The valine residue is moderately conserved and there is a small physicochemical difference between valine and leucine. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with STAT5B-related conditions. This variant is not present in population databases (ExAC no frequency).

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

Last Updated: Feb 28, 2024

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