NM_000257.4(MYH7):c.3286G>T (p.Asp1096Tyr) AND Primary dilated cardiomyopathy

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Nov 3, 2022
Review status:: criteria provided, conflicting classifications

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:: RCV000590886.10

Allele description [Variation Report for NM_000257.4(MYH7):c.3286G>T (p.Asp1096Tyr)]

NM_000257.4(MYH7):c.3286G>T (p.Asp1096Tyr)

Gene:

MYH7:myosin heavy chain 7 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q11.2

Genomic location:

Preferred name:

NM_000257.4(MYH7):c.3286G>T (p.Asp1096Tyr)

Other names:

NM_000257.3(MYH7):c.3286G>T

HGVS:

NC_000014.9:g.23421008C>A
NG_007884.1:g.19654G>T
NM_000257.4:c.3286G>TMANE SELECT
NP_000248.2:p.Asp1096Tyr
LRG_384t1:c.3286G>T
LRG_384:g.19654G>T
NC_000014.8:g.23890217C>A
NM_000257.2:c.3286G>T
NM_000257.3:c.3286G>T
c.3286G>T
p.D1096Y

Protein change:

D1096Y

Links:

dbSNP: rs45478699

NCBI 1000 Genomes Browser:

rs45478699

Molecular consequence:

NM_000257.4:c.3286G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Primary dilated cardiomyopathy (DCM)
Synonyms:: Dilated Cardiomyopathy
Identifiers:: EFO: EFO_0000407; MONDO: MONDO:0005021; MeSH: D002311; MedGen: C0007193; Human Phenotype Ontology: HP:0001644

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000059497	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely Benign (Nov 3, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19412328, 25031304, 25741868
SCV000700123	CSER _CC_NCGL, University of Washington - CSER - NEXT Medicine variant annotation	criteria provided, single submitter (Amendola et al. (Genome Res. 2015))	Likely pathogenic (Oct 1, 2016)	germline	research	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000059497

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely Benign
(Nov 3, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV000700123

CSER _CC_NCGL, University of Washington - CSER - NEXT Medicine variant annotation

criteria provided, single submitter

(Amendola et al. (Genome Res. 2015))

Likely pathogenic
(Oct 1, 2016)

germline

research

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	no	not provided	not provided	not provided	not provided	not provided	research
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Coding sequence mutations identified in MYH7, TNNT2, SCN5A, CSRP3, LBD3, and TCAP from 313 patients with familial or idiopathic dilated cardiomyopathy.

Hershberger RE, Parks SB, Kushner JD, Li D, Ludwigsen S, Jakobs P, Nauman D, Burgess D, Partain J, Litt M.

Clin Transl Sci. 2008 May;1(1):21-6. doi: 10.1111/j.1752-8062.2008.00017.x.

PubMed [citation]

PMID:: 19412328
PMCID:: PMC2633921

Sarcomere mutation-specific expression patterns in human hypertrophic cardiomyopathy.

Helms AS, Davis FM, Coleman D, Bartolone SN, Glazier AA, Pagani F, Yob JM, Sadayappan S, Pedersen E, Lyons R, Westfall MV, Jones R, Russell MW, Day SM.

Circ Cardiovasc Genet. 2014 Aug;7(4):434-43. doi: 10.1161/CIRCGENETICS.113.000448. Epub 2014 Jul 16.

PubMed [citation]

PMID:: 25031304
PMCID:: PMC4254656

See all PubMed Citations (4)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000059497.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The p.Asp1096Tyr variant in MYH7 has been previously reported in >3 individuals with DCM left ventricular hypertrophy (Hershberger 2008 PMID: 19412328, Helms 2014 PMID: 25031304, LMM data). This variant has also been identified in 0.026% (18/68042) European chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant was classified as Likely Benign on Mar 22, 2021 by the ClinGen-approved Cardiomyopathy variant curation expert panel (Variation ID 42953). Given the frequency, this variant is classified as likely benign. ACMG/AMP Criteria applied: BS1, PP3.

#	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 CSER _CC_NCGL, University of Washington - CSER - NEXT Medicine variant annotation, SCV000700123.1

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

Description

Found in patient having exome sequencing for an unrelated indication. No known history of dilated cardiomyopathy. This interpretation considers GERP score and allele frequency data, in addition to published reports of the variant in the literature, available at the time of review.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 23, 2024

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