NM_001378452.1(ITPR1):c.4333G>A (p.Val1445Met) AND ITPR1-related disorders

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 15, 2024
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:: RCV005250102.1

Allele description [Variation Report for NM_001378452.1(ITPR1):c.4333G>A (p.Val1445Met)]

NM_001378452.1(ITPR1):c.4333G>A (p.Val1445Met)

Gene:

ITPR1:inositol 1,4,5-trisphosphate receptor type 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p26.1

Genomic location:

Preferred name:

NM_001378452.1(ITPR1):c.4333G>A (p.Val1445Met)

HGVS:

NC_000003.12:g.4697198G>A
NG_016144.1:g.208851G>A
NM_001099952.4:c.4306G>A
NM_001168272.2:c.4288G>A
NM_001378452.1:c.4333G>AMANE SELECT
NM_002222.7:c.4261G>A
NP_001093422.2:p.Val1436Met
NP_001161744.1:p.Val1430Met
NP_001365381.1:p.Val1445Met
NP_002213.5:p.Val1421Met
NC_000003.11:g.4738882G>A
NM_001168272.1:c.4288G>A
NM_002222.5:c.4261G>A

Protein change:

V1421M

Links:

dbSNP: rs1559718601

NCBI 1000 Genomes Browser:

rs1559718601

Molecular consequence:

NM_001099952.4:c.4306G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001168272.2:c.4288G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001378452.1:c.4333G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002222.7:c.4261G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: ITPR1-related disorders
Identifiers:

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005900715	Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 15, 2024)	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

SCV005900715

Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Feb 15, 2024)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego, SCV005900715.1

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

Description

The ITPR1 gene is highly constrained (Z-score= 6.2 and pLI = 1), which suggests it is intolerant to variation. The c.4288G>A (p.Val1430Met) variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. This variant has not been previously reported or functionally characterized in the literature to our knowledge. The c.4288G>A (p.Val1430Met) variant is absent from the gnomAD population database and thus is presumed to be rare. Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, c.4288G>A (p.Val1430Met) is classified as Likely Pathogenic.

#	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: May 16, 2025

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