NM_002667.5(PLN):c.73C>G (p.Arg25Gly) AND Dilated cardiomyopathy 1P

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 4, 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:: RCV001852372.6

Allele description [Variation Report for NM_002667.5(PLN):c.73C>G (p.Arg25Gly)]

NM_002667.5(PLN):c.73C>G (p.Arg25Gly)

Genes:

CEP85L:centrosomal protein 85 like [Gene - OMIM - HGNC]
PLN:phospholamban [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6q22.31

Genomic location:

Preferred name:

NM_002667.5(PLN):c.73C>G (p.Arg25Gly)

Other names:

p.R25G:CGT>GGT

HGVS:

NC_000006.12:g.118558994C>G
NG_009082.1:g.15716C>G
NG_021248.1:g.156082G>C
NM_001042475.3:c.1020+6535G>CMANE SELECT
NM_001178035.2:c.1029+6535G>C
NM_002667.5:c.73C>GMANE SELECT
NM_206921.3:c.1020+6535G>C
NP_002658.1:p.Arg25Gly
NP_002658.1:p.Arg25Gly
LRG_390t1:c.73C>G
LRG_390:g.15716C>G
LRG_390p1:p.Arg25Gly
NC_000006.11:g.118880157C>G
NM_002667.3:c.73C>G

Protein change:

R25G

Links:

dbSNP: rs761056344

NCBI 1000 Genomes Browser:

rs761056344

Molecular consequence:

NM_001042475.3:c.1020+6535G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001178035.2:c.1029+6535G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_206921.3:c.1020+6535G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_002667.5:c.73C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Dilated cardiomyopathy 1P (CMD1P)
Identifiers:: MONDO: MONDO:0012362; MedGen: C1835928; Orphanet: 154; OMIM: 609909

Recent activity

Clear Turn Off Turn On

MULTISPECIES: 8-oxo-dGTP diphosphatase MutT [Basfia]
MULTISPECIES: 8-oxo-dGTP diphosphatase MutT [Basfia]
gi|499512870|ref|WP_011199510.1|

Protein
220 kDa polyprotein [African swine fever virus]
220 kDa polyprotein [African swine fever virus]
gi|9628199|ref|NP_042785.1|

Protein
Brassica juncea var. multiceps clone 3 internal transcribed spacer 1, partial se...
Brassica juncea var. multiceps clone 3 internal transcribed spacer 1, partial sequence; 5.8S ribosomal RNA gene, complete sequence; and internal transcribed spacer 2, partial sequence
gi|85001750|gb|DQ340647.1|

Nucleotide
zinc finger protein 9 (a cellular retroviral nucleic acid binding protein), isof...
zinc finger protein 9 (a cellular retroviral nucleic acid binding protein), isoform CRA_a [Homo sapiens]
gi|119599680|gb|EAW79274.1||gnl|WGS |hCP1781645

Protein
Cyprinella analostana voucher C3 small subunit ribosomal RNA gene, partial seque...
Cyprinella analostana voucher C3 small subunit ribosomal RNA gene, partial sequence; mitochondrial
gi|2282570912|gb|OP161448.1|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002144493	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 4, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 25691538, 25852082, 30012837, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002144493

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 4, 2023)

germline

clinical testing

PubMed (4)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Role of common and rare variants in SCN10A: results from the Brugada syndrome QRS locus gene discovery collaborative study.

Behr ER, Savio-Galimberti E, Barc J, Holst AG, Petropoulou E, Prins BP, Jabbari J, Torchio M, Berthet M, Mizusawa Y, Yang T, Nannenberg EA, Dagradi F, Weeke P, Bastiaenan R, Ackerman MJ, Haunso S, Leenhardt A, Kääb S, Probst V, Redon R, Sharma S, et al.

Cardiovasc Res. 2015 Jun 1;106(3):520-9. doi: 10.1093/cvr/cvv042. Epub 2015 Feb 17. Erratum in: Cardiovasc Res. 2016 May 1;110(1):3. doi: 10.1093/cvr/cvw038.

PubMed [citation]

PMID:: 25691538
PMCID:: PMC4447806

A novel human R25C-phospholamban mutation is associated with super-inhibition of calcium cycling and ventricular arrhythmia.

Liu GS, Morales A, Vafiadaki E, Lam CK, Cai WF, Haghighi K, Adly G, Hershberger RE, Kranias EG.

Cardiovasc Res. 2015 Jul 1;107(1):164-74. doi: 10.1093/cvr/cvv127. Epub 2015 Apr 7.

PubMed [citation]

PMID:: 25852082
PMCID:: PMC4490203

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002144493.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant is present in population databases (rs761056344, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 25 of the PLN protein (p.Arg25Gly). This variant has not been reported in the literature in individuals affected with PLN-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Arg25 amino acid residue in PLN. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25691538, 25852082, 30012837; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 202038).

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine