NM_181523.3(PIK3R1):c.1703C>A (p.Pro568Gln) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 10, 2023
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:: RCV003812507.1

Allele description [Variation Report for NM_181523.3(PIK3R1):c.1703C>A (p.Pro568Gln)]

NM_181523.3(PIK3R1):c.1703C>A (p.Pro568Gln)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

5q13.1

Genomic location:

Preferred name:

NM_181523.3(PIK3R1):c.1703C>A (p.Pro568Gln)

HGVS:

NC_000005.10:g.68295282C>A
NG_012849.2:g.84527C>A
NM_001242466.2:c.614C>A
NM_181504.4:c.893C>A
NM_181523.3:c.1703C>AMANE SELECT
NM_181524.2:c.803C>A
NP_001229395.1:p.Pro205Gln
NP_852556.2:p.Pro298Gln
NP_852664.1:p.Pro568Gln
NP_852664.1:p.Pro568Gln
NP_852665.1:p.Pro268Gln
LRG_453t1:c.1703C>A
LRG_453:g.84527C>A
LRG_453p1:p.Pro568Gln
NC_000005.9:g.67591110C>A
NM_181523.1:c.1703C>A

Protein change:

P205Q

Molecular consequence:

NM_001242466.2:c.614C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_181504.4:c.893C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_181523.3:c.1703C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_181524.2:c.803C>A - missense variant - [Sequence Ontology: SO:0001583]

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

Name:: Agammaglobulinemia 7, autosomal recessive (AGM7)
Synonyms:: AGAMMAGLOBULINEMIA, AUTOSOMAL RECESSIVE, DUE TO PIK3R1 DEFECT
Identifiers:: MONDO: MONDO:0014083; MedGen: C3554689; OMIM: 615214

Name:: Immunodeficiency 36 (IMD36)
Synonyms:: IMMUNODEFICIENCY 36 WITH LYMPHOPROLIFERATION
Identifiers:: MONDO: MONDO:0014453; MedGen: C4014934; Orphanet: 397596; OMIM: 616005

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004608152	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 10, 2023)	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

SCV004608152

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 10, 2023)

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, SCV004608152.1

#	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 proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 568 of the PIK3R1 protein (p.Pro568Gln). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PIK3R1-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PIK3R1 protein function. 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.

#	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: Mar 5, 2024

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