NM_032578.4(MYPN):c.3127del (p.Ser1043fs) AND Dilated cardiomyopathy 1KK

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 8, 2024
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:: RCV000818659.4

Allele description [Variation Report for NM_032578.4(MYPN):c.3127del (p.Ser1043fs)]

NM_032578.4(MYPN):c.3127del (p.Ser1043fs)

Gene:

MYPN:myopalladin [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

10q21.3

Genomic location:

Preferred name:

NM_032578.4(MYPN):c.3127del (p.Ser1043fs)

HGVS:

NC_000010.11:g.68195501del
NG_032118.1:g.94385del
NM_001256267.2:c.3127del
NM_001256268.2:c.2245del
NM_032578.4:c.3127delMANE SELECT
NP_001243196.1:p.Ser1043fs
NP_001243197.1:p.Ser749fs
NP_115967.2:p.Ser1043fs
LRG_410:g.94385del
NC_000010.10:g.69955258del
NM_032578.3:c.3127delA
NR_045662.4:n.2664del
NR_045663.4:n.3201del

Protein change:

S1043fs

Links:

dbSNP: rs1589608098

NCBI 1000 Genomes Browser:

rs1589608098

Molecular consequence:

NM_001256267.2:c.3127del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001256268.2:c.2245del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_032578.4:c.3127del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_045662.4:n.2664del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_045663.4:n.3201del - 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
SCV000959284	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 8, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28017374, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000959284

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 8, 2024)

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

Biallelic Mutations in MYPN, Encoding Myopalladin, Are Associated with Childhood-Onset, Slowly Progressive Nemaline Myopathy.

Miyatake S, Mitsuhashi S, Hayashi YK, Purevjav E, Nishikawa A, Koshimizu E, Suzuki M, Yatabe K, Tanaka Y, Ogata K, Kuru S, Shiina M, Tsurusaki Y, Nakashima M, Mizuguchi T, Miyake N, Saitsu H, Ogata K, Kawai M, Towbin J, Nonaka I, Nishino I, et al.

Am J Hum Genet. 2017 Jan 5;100(1):169-178. doi: 10.1016/j.ajhg.2016.11.017. Epub 2016 Dec 22.

PubMed [citation]

PMID:: 28017374
PMCID:: PMC5223057

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 Invitae, SCV000959284.4

#	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 creates a premature translational stop signal (p.Ser1043Valfs*3) in the MYPN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYPN are known to be pathogenic (PMID: 28017374). This variant is not present in population databases (gnomAD no frequency). 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: 661274). For these reasons, this variant has been classified as Pathogenic.

#	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: Feb 20, 2024

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