NM_004415.4(DSP):c.3134G>A (p.Arg1045Gln) AND Cardiomyopathy

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 16, 2020
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:: RCV000852571.3

Allele description [Variation Report for NM_004415.4(DSP):c.3134G>A (p.Arg1045Gln)]

NM_004415.4(DSP):c.3134G>A (p.Arg1045Gln)

Gene:

DSP:desmoplakin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p24.3

Genomic location:

Preferred name:

NM_004415.4(DSP):c.3134G>A (p.Arg1045Gln)

HGVS:

NC_000006.12:g.7579324G>A
NG_008803.1:g.42688G>A
NM_001008844.3:c.3134G>A
NM_001319034.2:c.3134G>A
NM_004415.4:c.3134G>AMANE SELECT
NP_001008844.1:p.Arg1045Gln
NP_001305963.1:p.Arg1045Gln
NP_004406.2:p.Arg1045Gln
LRG_423t1:c.3134G>A
LRG_423:g.42688G>A
NC_000006.11:g.7579557G>A
NM_004415.2:c.3134G>A

Protein change:

R1045Q

Links:

dbSNP: rs374263890

NCBI 1000 Genomes Browser:

rs374263890

Molecular consequence:

NM_001008844.3:c.3134G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001319034.2:c.3134G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004415.4:c.3134G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Cardiomyopathy (CMYO)
Synonyms:: Cardiomyopathies
Identifiers:: MONDO: MONDO:0004994; MedGen: C0878544; Human Phenotype Ontology: HP:0001638

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Bpnt1 3'(2'), 5'-bisphosphate nucleotidase 1 [Mus musculus]
Bpnt1 3'(2'), 5'-bisphosphate nucleotidase 1 [Mus musculus]
Gene ID:23827

Gene
23827[uid] AND (alive[prop]) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000995272	Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 26, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001734468	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 16, 2020)	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

SCV000995272

Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 26, 2018)

germline

clinical testing

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

SCV001734468

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Sep 16, 2020)

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	not provided	not provided	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 Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego, SCV000995272.1

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

From Color Diagnostics, LLC DBA Color Health, SCV001734468.1

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

Description

This missense variant replaces arginine with glutamine at codon 1045 of the DSP protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 12/282294 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#	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: Oct 20, 2024

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