NM_020433.5(JPH2):c.1213G>A (p.Ala405Thr) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 21, 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:: RCV000617750.4

Allele description [Variation Report for NM_020433.5(JPH2):c.1213G>A (p.Ala405Thr)]

NM_020433.5(JPH2):c.1213G>A (p.Ala405Thr)

Gene:

JPH2:junctophilin 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20q13.12

Genomic location:

Preferred name:

NM_020433.5(JPH2):c.1213G>A (p.Ala405Thr)

HGVS:

NC_000020.11:g.44118580C>T
NG_031867.1:g.73999G>A
NM_020433.5:c.1213G>AMANE SELECT
NP_065166.2:p.Ala405Thr
NP_065166.2:p.Ala405Thr
LRG_394t1:c.1213G>A
LRG_394:g.73999G>A
LRG_394p1:p.Ala405Thr
NC_000020.10:g.42747220C>T
NM_020433.4:c.1213G>A

Protein change:

A405T

Links:

dbSNP: rs557878787

NCBI 1000 Genomes Browser:

rs557878787

Molecular consequence:

NM_020433.5:c.1213G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000740032	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Feb 21, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23973696, 28087566, 35026164 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000740032

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Feb 21, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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

Mutation E169K in junctophilin-2 causes atrial fibrillation due to impaired RyR2 stabilization.

Beavers DL, Wang W, Ather S, Voigt N, Garbino A, Dixit SS, Landstrom AP, Li N, Wang Q, Olivotto I, Dobrev D, Ackerman MJ, Wehrens XHT.

J Am Coll Cardiol. 2013 Nov 19;62(21):2010-9. doi: 10.1016/j.jacc.2013.06.052. Epub 2013 Aug 21.

PubMed [citation]

PMID:: 23973696
PMCID:: PMC3830688

Application of Whole Exome Sequencing in the Clinical Diagnosis and Management of Inherited Cardiovascular Diseases in Adults.

Seidelmann SB, Smith E, Subrahmanyan L, Dykas D, Abou Ziki MD, Azari B, Hannah-Shmouni F, Jiang Y, Akar JG, Marieb M, Jacoby D, Bale AE, Lifton RP, Mani A.

Circ Cardiovasc Genet. 2017 Feb;10(1). doi:pii: e001573. 10.1161/CIRCGENETICS.116.001573.

PubMed [citation]

PMID:: 28087566
PMCID:: PMC5245580

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000740032.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The p.A405T variant (also known as c.1213G>A), located in coding exon 3 of the JPH2 gene, results from a G to A substitution at nucleotide position 1213. The alanine at codon 405 is replaced by threonine, an amino acid with similar properties. This alteration has been reported in a subject with hypertrophic cardiomyopathy (Seidelmann SB et al. Circ Cardiovasc Genet. 2017; Feb;10(1)). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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 1, 2024

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