NM_181523.3(PIK3R1):c.1612ATT[1] (p.Ile539del) AND SHORT syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jul 11, 2013
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:: RCV000054532.32

Allele description [Variation Report for NM_181523.3(PIK3R1):c.1612ATT[1] (p.Ile539del)]

NM_181523.3(PIK3R1):c.1612ATT[1] (p.Ile539del)

Gene:

PIK3R1:phosphoinositide-3-kinase regulatory subunit 1 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

5q13.1

Genomic location:

Preferred name:

NM_181523.3(PIK3R1):c.1612ATT[1] (p.Ile539del)

HGVS:

NC_000005.10:g.68295191ATT[1]
NG_012849.2:g.84436ATT[1]
NM_001242466.2:c.523ATT[1]
NM_181504.4:c.802ATT[1]
NM_181523.3:c.1612ATT[1]MANE SELECT
NM_181524.2:c.712ATT[1]
NP_001229395.1:p.Ile176del
NP_852556.2:p.Ile269del
NP_852664.1:p.Ile539del
NP_852665.1:p.Ile239del
LRG_453t1:c.1612ATT[1]
LRG_453:g.84436ATT[1]
LRG_453p1:p.Ile539del
NC_000005.9:g.67591019ATT[1]
NM_181523.2:c.1615_1617delATT

Protein change:

I176del; ILE539DEL

Links:

OMIM: 171833.0002; dbSNP: rs397514046

NCBI 1000 Genomes Browser:

rs397514046

Molecular consequence:

NM_001242466.2:c.523ATT[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_181504.4:c.802ATT[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_181523.3:c.1612ATT[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_181524.2:c.712ATT[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Name:: SHORT syndrome
Synonyms:: SHORT STATURE, HYPEREXTENSIBILITY, HERNIA, OCULAR DEPRESSION, RIEGER ANOMALY, AND TEETHING DELAY; Stature, Hyperextensibility of joints or Hernia (inguinal), Ocular depression, Rieger anomaly and Teething delay; LIPODYSTROPHY, PARTIAL, WITH RIEGER ANOMALY AND SHORT STATURE
Identifiers:: MONDO: MONDO:0010026; MedGen: C0878684; Orphanet: 3163; OMIM: 269880

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000083010	OMIM	no assertion criteria provided	Pathogenic (Jul 11, 2013)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000148011	GeneReviews	no classification provided	not provided	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

SCV000083010

OMIM

no assertion criteria provided

Pathogenic
(Jul 11, 2013)

germline

literature only

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

SCV000148011

GeneReviews

no classification provided

not provided

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
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

PIK3R1 mutations cause syndromic insulin resistance with lipoatrophy.

Thauvin-Robinet C, Auclair M, Duplomb L, Caron-Debarle M, Avila M, St-Onge J, Le Merrer M, Le Luyer B, Héron D, Mathieu-Dramard M, Bitoun P, Petit JM, Odent S, Amiel J, Picot D, Carmignac V, Thevenon J, Callier P, Laville M, Reznik Y, Fagour C, Nunes ML, et al.

Am J Hum Genet. 2013 Jul 11;93(1):141-9. doi: 10.1016/j.ajhg.2013.05.019. Epub 2013 Jun 27.

PubMed [citation]

PMID:: 23810378
PMCID:: PMC3710759

Details of each submission

From OMIM, SCV000083010.3

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

Description

In a 7-year-old boy with SHORT syndrome (269880), Thauvin-Robinet et al. (2013) identified heterozygosity for a de novo 3-bp deletion (c.1615_1617delATT) at chr5:67,591,018 (GRCh37) in the PIK3R1 gene, resulting in deletion of ile539 in the inter-Src homology 2 (iSH2) domain. The mutation was not present in his unaffected parents and was not found in the NHLBI Exome Variant Server, dbSNP (build 137), or 1000 Genomes Project databases. Functional studies on patient fibroblasts revealed a 70 to 90% reduction in the effect of insulin on AKT (see 164730) activation, glycogen synthesis, and glucose uptake, indicating severe insulin resistance for both proximal and distal PI3K-dependent signaling.

#	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

From GeneReviews, SCV000148011.2

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

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

Last Updated: Jun 9, 2024

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