NM_000257.4(MYH7):c.4348G>A (p.Asp1450Asn) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 12, 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:: RCV002326730.3

Allele description [Variation Report for NM_000257.4(MYH7):c.4348G>A (p.Asp1450Asn)]

NM_000257.4(MYH7):c.4348G>A (p.Asp1450Asn)

Genes:

MYH7:myosin heavy chain 7 [Gene - OMIM - HGNC]
MHRT:myosin heavy chain associated RNA transcript [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q11.2

Genomic location:

Preferred name:

NM_000257.4(MYH7):c.4348G>A (p.Asp1450Asn)

HGVS:

NC_000014.9:g.23417508C>T
NG_007884.1:g.23154G>A
NM_000257.4:c.4348G>AMANE SELECT
NP_000248.2:p.Asp1450Asn
LRG_384t1:c.4348G>A
LRG_384:g.23154G>A
NC_000014.8:g.23886717C>T
NM_000257.2:c.4348G>A
NM_000257.3:c.4348G>A
c.4348G>A

Protein change:

D1450N

Links:

dbSNP: rs397516211

NCBI 1000 Genomes Browser:

rs397516211

Molecular consequence:

NM_000257.4:c.4348G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002627901	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Dec 12, 2023)	germline	clinical testing	PubMed (13) [See all records that cite these PMIDs] 22464770, 24503780, 27532257, 27600940, 28606303, 31638223, 32746448, 32815737, 33297573, 33996946, 34542152, 35050212, 35626289 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002627901

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Dec 12, 2023)

germline

clinical testing

PubMed (13)
[See all records that cite these PMIDs]

Citation Link

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

Genetic testing for dilated cardiomyopathy in clinical practice.

Lakdawala NK, Funke BH, Baxter S, Cirino AL, Roberts AE, Judge DP, Johnson N, Mendelsohn NJ, Morel C, Care M, Chung WK, Jones C, Psychogios A, Duffy E, Rehm HL, White E, Seidman JG, Seidman CE, Ho CY.

J Card Fail. 2012 Apr;18(4):296-303. doi: 10.1016/j.cardfail.2012.01.013. Epub 2012 Feb 15.

PubMed [citation]

PMID:: 22464770
PMCID:: PMC3666099

The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing.

Pugh TJ, Kelly MA, Gowrisankar S, Hynes E, Seidman MA, Baxter SM, Bowser M, Harrison B, Aaron D, Mahanta LM, Lakdawala NK, McDermott G, White ET, Rehm HL, Lebo M, Funke BH.

Genet Med. 2014 Aug;16(8):601-8. doi: 10.1038/gim.2013.204. Epub 2014 Feb 6.

PubMed [citation]

PMID:: 24503780

See all PubMed Citations (13)

Details of each submission

From Ambry Genetics, SCV002627901.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (13)

Description

The p.D1450N variant (also known as c.4348G>A), located in coding exon 29 of the MYH7 gene, results from a G to A substitution at nucleotide position 4348. The aspartic acid at codon 1450 is replaced by asparagine, an amino acid with highly similar properties. This alteration has been reported in both dilated cardiomyopathy and hypertrophic cardiomyopathy cohorts; however, clinical details were limited in some cases (Lakdawala NK et al. J. Card. Fail. 2012;18:296-303; Cecconi M et al. Int. J. Mol. Med. 2016;38:1111-24; Alamo L et al. Elife, 2017 06;6; Wang B et al. Mol Med Rep, 2019 Dec;20:5229-5238; Micheu MM et al. Diagnostics (Basel), 2020 Dec;10; Burstein DS et al. Pediatr Res, 2021 05;89:1470-1476; Pezzoli L et al. J Cardiovasc Dev Dis, 2021 Dec;9; Sepp R et al. Diagnostics (Basel). 2022 May;12(5); Ambry internal data). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: Nov 3, 2024

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