NM_001378452.1(ITPR1):c.805C>T (p.Arg269Trp) AND Spinocerebellar ataxia type 15/16

Germline classification:: Pathogenic (2 submissions)
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:: RCV003335291.2

Allele description [Variation Report for NM_001378452.1(ITPR1):c.805C>T (p.Arg269Trp)]

NM_001378452.1(ITPR1):c.805C>T (p.Arg269Trp)

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.805C>T (p.Arg269Trp)

HGVS:

NC_000003.12:g.4645678C>T
NG_016144.1:g.157331C>T
NM_001099952.4:c.805C>T
NM_001168272.2:c.805C>T
NM_001378452.1:c.805C>TMANE SELECT
NM_002222.7:c.805C>T
NP_001093422.2:p.Arg269Trp
NP_001161744.1:p.Arg269Trp
NP_001161744.1:p.Arg269Trp
NP_001365381.1:p.Arg269Trp
NP_002213.5:p.Arg269Trp
NC_000003.11:g.4687362C>T
NM_001168272.1:c.805C>T
NM_001378452.1:c.805C>T
NM_002222.5:c.805C>T
p.Arg269Trp

Protein change:

R269W

Links:

dbSNP: rs886039392

NCBI 1000 Genomes Browser:

rs886039392

Molecular consequence:

NM_001099952.4:c.805C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001168272.2:c.805C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001378452.1:c.805C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002222.7:c.805C>T - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

loss_of_function_variant [Sequence Ontology: SO:0002054]

Condition(s)

Name:: Spinocerebellar ataxia type 15/16 (SCA15)
Synonyms:: SCA16 (formerly); Spinocerebellar ataxia 16 (formerly); Spinocerebellar Ataxia Type 15; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011694; MedGen: C1847725; OMIM: 606658

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004046252	Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005091239	Solve-RD Consortium	no assertion criteria provided	Likely pathogenic (Jun 1, 2022)	inherited	provider interpretation

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004046252

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

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

clinical testing

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

SCV005091239

Solve-RD Consortium

no assertion criteria provided

Likely pathogenic
(Jun 1, 2022)

inherited

provider interpretation

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
not provided	inherited	yes	not provided	not provided	not provided	not provided	not provided	provider interpretation

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, SCV004046252.1

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

Description

This variant has been previously reported as a heterozygous de novo (or suspected de novo) variant in numerous individuals with Spinocerebellar Ataxia 15 (PMID: 27062503, 25533962, 28826917, 28191890, 28135719, 28659154, 29925855, 31216405, 33258288). It is absent from the gnomAD population database and thus is presumed to be rare. The c.805C>T (p.Arg269Trp) variant is predicted by multiple in silico tools to have a deleterious effect on protein function. 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, the c.805C>T (p.Arg269Trp) variant is classified as 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

From Solve-RD Consortium, SCV005091239.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	provider interpretation	not provided

Description

Variant confirmed as disease-causing by referring clinical team

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

Last Updated: Jan 13, 2025

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