NM_032578.4(MYPN):c.3833G>A (p.Arg1278Gln) AND MYPN-related myopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 25, 2020
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:: RCV002470788.2

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:: MYPN-related myopathy (CMYO24)
Synonyms:: Nemaline myopathy 11, autosomal recessive
Identifiers:: MONDO: MONDO:0015023; MedGen: C4479186; OMIM: 617336

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002768584	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 25, 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

SCV002768584

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 25, 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	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 Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002768584.1

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

Description

A heterozygous missense variant was identified, NM_032578.3(MYPN):c.3833G>A in exon 20 of 20 of the MYPN gene. This substitution is predicted to create a minor amino acid change from arginine to glutamine at position 1278 of the protein, NP_115967.2(MYPN):p.(Arg1278Gln). The arginine at this position has high conservation (100 vertebrates, UCSC), but is not situated in a known functional domain. In silico software predicts this variant to be disease causing (Polyphen, SIFT, CADD, Mutation Taster). The variant is present in the gnomAD population database at a frequency of 0.045% (127 heterozygotes, 0 homozygotes). Two alternative residue changes at the same location have been reported in the gnomAD database at a frequency of 0.0008% and 0.0012% respectively. It has been previously reported as a VUS in patients with a cardiovascular phenotype (ClinVar). Based on information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE (VUS).

#	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		not provided	not provided	not provided	not provided

Last Updated: Nov 24, 2024

ClinVar

Relating variation to medicine