NM_002667.5(PLN):c.152T>C (p.Leu51Pro) AND Dilated cardiomyopathy 1P

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 18, 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:: RCV002513479.3

Allele description [Variation Report for NM_002667.5(PLN):c.152T>C (p.Leu51Pro)]

NM_002667.5(PLN):c.152T>C (p.Leu51Pro)

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.152T>C (p.Leu51Pro)

HGVS:

NC_000006.12:g.118559073T>C
NG_009082.1:g.15795T>C
NG_021248.1:g.156003A>G
NM_001042475.3:c.1020+6456A>GMANE SELECT
NM_001178035.2:c.1029+6456A>G
NM_002667.5:c.152T>CMANE SELECT
NM_206921.3:c.1020+6456A>G
NP_002658.1:p.Leu51Pro
NP_002658.1:p.Leu51Pro
LRG_390t1:c.152T>C
LRG_390:g.15795T>C
LRG_390p1:p.Leu51Pro
NC_000006.11:g.118880236T>C
NM_002667.3:c.152T>C
c.152T>C

Protein change:

L51P

Links:

dbSNP: rs397516783

NCBI 1000 Genomes Browser:

rs397516783

Molecular consequence:

NM_001042475.3:c.1020+6456A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001178035.2:c.1029+6456A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_206921.3:c.1020+6456A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_002667.5:c.152T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003440009	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 18, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27532257, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003440009

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 18, 2022)

germline

clinical testing

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, Mazzarotto F, Blair E, Seller A, Taylor JC, Minikel EV, Exome Aggregation Consortium, MacArthur DG, Farrall M, Cook SA, Watkins H.

Genet Med. 2017 Feb;19(2):192-203. doi: 10.1038/gim.2016.90. Epub 2016 Aug 17.

PubMed [citation]

PMID:: 27532257
PMCID:: PMC5116235

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003440009.2

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

Description

This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 51 of the PLN protein (p.Leu51Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 44577). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.

#	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

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