NM_020433.5(JPH2):c.1282C>T (p.Gln428Ter) AND Cardiomyopathy, dilated, 2E

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Feb 23, 2022
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:: RCV001572616.2

Allele description [Variation Report for NM_020433.5(JPH2):c.1282C>T (p.Gln428Ter)]

NM_020433.5(JPH2):c.1282C>T (p.Gln428Ter)

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.1282C>T (p.Gln428Ter)

HGVS:

NC_000020.11:g.44118511G>A
NG_031867.1:g.74068C>T
NM_020433.5:c.1282C>TMANE SELECT
NP_065166.2:p.Gln428Ter
NP_065166.2:p.Gln428Ter
LRG_394t1:c.1282C>T
LRG_394:g.74068C>T
LRG_394p1:p.Gln428Ter
NC_000020.10:g.42747151G>A
NM_020433.4:c.1282C>T

Protein change:

Q428*; GLN428TER

Links:

OMIM: 605267.0005; dbSNP: rs199896820

NCBI 1000 Genomes Browser:

rs199896820

Molecular consequence:

NM_020433.5:c.1282C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Cardiomyopathy, dilated, 2E
Identifiers:: MONDO: MONDO:0030366; MedGen: C5561970; OMIM: 619492

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001797289	OMIM	no assertion criteria provided	Pathogenic (Aug 18, 2021)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002319194	SIB Swiss Institute of Bioinformatics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 23, 2022)	unknown	curation	PubMed (2) [See all records that cite these PMIDs] 30384889, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001797289

OMIM

no assertion criteria provided

Pathogenic
(Aug 18, 2021)

germline

literature only

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

SCV002319194

SIB Swiss Institute of Bioinformatics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Feb 23, 2022)

unknown

curation

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

Genetic Basis of Severe Childhood-Onset Cardiomyopathies.

Vasilescu C, Ojala TH, Brilhante V, Ojanen S, Hinterding HM, Palin E, Alastalo TP, Koskenvuo J, Hiippala A, Jokinen E, Jahnukainen T, Lohi J, Pihkala J, Tyni TA, Carroll CJ, Suomalainen A.

J Am Coll Cardiol. 2018 Nov 6;72(19):2324-2338. doi: 10.1016/j.jacc.2018.08.2171.

PubMed [citation]

PMID:: 30384889

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 OMIM, SCV001797289.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a 22.5-year-old Finnish woman (P10) who was diagnosed with dilated cardiomyopathy (CMD2E; 619492) at 3 years of age and underwent cardiac transplantation at age 4, Vasilescu et al. (2018) identified homozygosity for a c.1282C-T transition in the JPH2 gene, resulting in a gln428-to-ter (Q428X) substitution. Her unaffected parents and 2 unaffected sibs were heterozygous for the mutation. Functional studies of the variant or of patient cells were not performed. The authors' criteria for causative recessive variants were a minor allele frequency of less than or equal to 0.01 in the ExAC, gnomAD, and SISu databases, and presence only in heterozygosity; the exact frequency for this variant was not published.

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

From SIB Swiss Institute of Bioinformatics, SCV002319194.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (2)

Description

This variant is interpreted as a variant of uncertain significance for Cardiomyopathy, dilated, 2E, autosomal recessive. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); Predicted nullvariant in a gene where LOF is a known mechanism of disease (PVS1 downgraded to moderate).

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

Last Updated: Nov 10, 2024

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