NM_000540.3(RYR1):c.12355A>T (p.Asn4119Tyr) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Jul 11, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000119459.6

Allele description [Variation Report for NM_000540.3(RYR1):c.12355A>T (p.Asn4119Tyr)]

NM_000540.3(RYR1):c.12355A>T (p.Asn4119Tyr)

Gene:

RYR1:ryanodine receptor 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19q13.2

Genomic location:

Preferred name:

NM_000540.3(RYR1):c.12355A>T (p.Asn4119Tyr)

HGVS:

NC_000019.10:g.38561185A>T
NG_008866.1:g.132486A>T
NM_000540.3:c.12355A>TMANE SELECT
NM_001042723.2:c.12340A>T
NP_000531.2:p.Asn4119Tyr
NP_000531.2:p.Asn4119Tyr
NP_001036188.1:p.Asn4114Tyr
LRG_766t1:c.12355A>T
LRG_766:g.132486A>T
LRG_766p1:p.Asn4119Tyr
NC_000019.9:g.39051825A>T
NM_000540.2(RYR1):c.12355A>T
NM_000540.2:c.12355A>T
p.(Asn4119Tyr)
p.Asn4119Tyr

Protein change:

N4114Y

Links:

dbSNP: rs193922848

NCBI 1000 Genomes Browser:

rs193922848

Molecular consequence:

NM_000540.3:c.12355A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001042723.2:c.12340A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000154366	RYR1 database	no classification provided	not provided	unknown	not provided
SCV003812544	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Dec 10, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004031814	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jul 11, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000154366

RYR1 database

no classification provided

not provided

unknown

not provided

SCV003812544

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Dec 10, 2019)

germline

clinical testing

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

SCV004031814

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Jul 11, 2023)

germline

clinical testing

Citation Link

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	unknown	not provided	not provided	not provided	not provided	1	not provided	literature only
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 RYR1 database, SCV000154366.1

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

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

From Revvity Omics, Revvity, SCV003812544.2

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

#	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

From GeneDx, SCV004031814.1

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

Description

Published functional studies found this variant was associated with calcium and magnesium dependent channel regulation that was not significantly different than wild-type (Gomez AC et al., 2016); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as p.(N4120Y); This variant is associated with the following publications: (PMID: 15731587, 16115682, 27558158)

#	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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