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NM_000257.4(MYH7):c.3286G>T (p.Asp1096Tyr) AND Hypertrophic cardiomyopathy 1

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 30, 2015
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:
RCV000201875.9

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:
Hypertrophic cardiomyopathy 1
Synonyms:
Familial hypertrophic cardiomyopathy 1; MYH7-Related Familial Hypertrophic Cardiomyopathy
Identifiers:
MONDO: MONDO:0008647; MedGen: C3495498; OMIM: 192600

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000256636Agnes Ginges Centre for Molecular Cardiology, Centenary Institute
criteria provided, single submitter

(Agnes Ginges Centre for Molecular Cardiology criteria (2015))		Uncertain significance
(Jul 30, 2015) 		germlineresearch

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot provided1not providednot providednot providedresearch

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

Details of each submission

From Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, SCV000256636.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (2)

Description

The Asp1096Tyr variant in MYH7 has been previously reported by Hershberger et al (2008) in 2 DCM probands. Helms et al (2014) analysed sarcomere transcript and protein levels in septal myectomy and transplant specimens from genotyped HCM patients - one of whome carried this MYH Asp1096Tyr variant. This variant has been reported with an allele frequency of 0.0001 (18/66,720 European non-Finnish alleles and 1/908 'other') in the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/). The MYH7 Asp1096Tyr variant occurs in a conserved region, and in-silico tools (SIFT, PolyPhen, MutationTaster and CADD) support a damaging role for this variant, however this alone is not strong evidence for pathogenicity. We have identified this variant in 1 HCM proband who presented in her 30's with asymmetric hypertrophy (IVS 21mm) and obstruction. This proband experienced a sudden cardiac death in her 50s. It is noted that this proband also carried a pathogenic MYBPC3 nonsense variant. Based on the limited reports in the literature, and our finding of MYH7 Asp1096Tyr in an isolated HCM case who carried an additional variant which is known to be disease-causing, we have classified this variant as having "uncertain significance". Additional evidence is required to fully establish its pathogenic role.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot provided1not provided

Last Updated: Nov 10, 2024