NM_032578.4(MYPN):c.3833G>A (p.Arg1278Gln) AND Dilated cardiomyopathy 1KK

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 22, 2024
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:: RCV000230154.15

Allele description [Variation Report for NM_032578.4(MYPN):c.3833G>A (p.Arg1278Gln)]

NM_032578.4(MYPN):c.3833G>A (p.Arg1278Gln)

Gene:

MYPN:myopalladin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q21.3

Genomic location:

Preferred name:

NM_032578.4(MYPN):c.3833G>A (p.Arg1278Gln)

HGVS:

NC_000010.11:g.68210325G>A
NG_032118.1:g.109209G>A
NM_001256267.2:c.3833G>A
NM_001256268.2:c.2951G>A
NM_032578.4:c.3833G>AMANE SELECT
NP_001243196.1:p.Arg1278Gln
NP_001243196.1:p.Arg1278Gln
NP_001243197.1:p.Arg984Gln
NP_115967.2:p.Arg1278Gln
NP_115967.2:p.Arg1278Gln
LRG_410t1:c.3833G>A
LRG_410:g.109209G>A
LRG_410p1:p.Arg1278Gln
NC_000010.10:g.69970082G>A
NM_001256267.1:c.3833G>A
NM_032578.2:c.3833G>A
NM_032578.3:c.3833G>A
NR_045662.4:n.3370G>A
NR_045663.4:n.3907G>A

Protein change:

R1278Q

Links:

dbSNP: rs142877365

NCBI 1000 Genomes Browser:

rs142877365

Molecular consequence:

NM_001256267.2:c.3833G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001256268.2:c.2951G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_032578.4:c.3833G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_045662.4:n.3370G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_045663.4:n.3907G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Dilated cardiomyopathy 1KK (CMD1KK)
Identifiers:: MONDO: MONDO:0014100; MedGen: C3714995; Orphanet: 154; Orphanet: 75249; OMIM: 615248

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000291124	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 22, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001366450	Centre for Mendelian Genomics, University Medical Centre Ljubljana	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 1, 2016)	unknown	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

SCV000291124

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 22, 2024)

germline

clinical testing

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

SCV001366450

Centre for Mendelian Genomics, University Medical Centre Ljubljana

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 1, 2016)

unknown

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	unknown	yes	not provided	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

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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000291124.11

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

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1278 of the MYPN protein (p.Arg1278Gln). This variant is present in population databases (rs142877365, gnomAD 0.08%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with MYPN-related conditions. ClinVar contains an entry for this variant (Variation ID: 191759). 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. 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

From Centre for Mendelian Genomics, University Medical Centre Ljubljana, SCV001366450.2

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

Description

This variant was classified as: Uncertain significance. The following ACMG criteria were applied in classifying this variant: PP3,PP4.

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

Last Updated: Nov 30, 2024

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