NM_001378452.1(ITPR1):c.755C>T (p.Thr252Ile) AND Spinocerebellar ataxia type 29

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Mar 22, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV001358678.3

Allele description [Variation Report for NM_001378452.1(ITPR1):c.755C>T (p.Thr252Ile)]

NM_001378452.1(ITPR1):c.755C>T (p.Thr252Ile)

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.755C>T (p.Thr252Ile)

HGVS:

NC_000003.12:g.4645628C>T
NG_016144.1:g.157281C>T
NM_001099952.4:c.755C>T
NM_001168272.2:c.755C>T
NM_001378452.1:c.755C>TMANE SELECT
NM_002222.7:c.755C>T
NP_001093422.2:p.Thr252Ile
NP_001161744.1:p.Thr252Ile
NP_001365381.1:p.Thr252Ile
NP_002213.5:p.Thr252Ile
NC_000003.11:g.4687312C>T
NM_001378452.1:c.755C>T

Protein change:

T252I

Links:

dbSNP: rs2125159718

NCBI 1000 Genomes Browser:

rs2125159718

Molecular consequence:

NM_001099952.4:c.755C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001168272.2:c.755C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001378452.1:c.755C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002222.7:c.755C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Spinocerebellar ataxia type 29 (SCA29)
Synonyms:: Cerebellar ataxia early-onset nonprogressive; CEREBELLAR ATAXIA, CONGENITAL NONPROGRESSIVE, AUTOSOMAL DOMINANT; Spinocerebellar ataxia 29, congenital nonprogressive
Identifiers:: MONDO: MONDO:0007298; MedGen: C1861732; Orphanet: 208513; OMIM: 117360

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001554479	Centre for Inherited Metabolic Diseases, Karolinska University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 7, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005045129	Clinical Genomics Laboratory, Washington University in St. Louis	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 22, 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

SCV001554479

Centre for Inherited Metabolic Diseases, Karolinska University Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 7, 2021)

germline

clinical testing

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

SCV005045129

Clinical Genomics Laboratory, Washington University in St. Louis

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 22, 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	1	not provided	not provided	1	no	clinical testing
not provided	germline	unknown	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 Centre for Inherited Metabolic Diseases, Karolinska University Hospital, SCV001554479.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	no	clinical testing	PubMed (1)

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

From Clinical Genomics Laboratory, Washington University in St. Louis, SCV005045129.1

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

Description

The ITPR1 c.755C>T (p.Thr252Ile) variant, to our knowledge, has not been reported in the medical literature and is absent from the general population (gnomAD v.2.1.1), indicating it is not a common variant. Computational predictors indicate that the variant is damaging, evidence that correlates with impact to ITPR1 function. This variant has been reported in the ClinVar database as a germline likely pathogenic variant by one submitter. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain at this time.

#	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: May 26, 2024

ClinVar

Relating variation to medicine