NM_000257.4(MYH7):c.740T>G (p.Phe247Cys) AND Cardiovascular phenotype

Clinical significance:Likely pathogenic (Last evaluated: Mar 29, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000620575.2

Allele description [Variation Report for NM_000257.4(MYH7):c.740T>G (p.Phe247Cys)]

NM_000257.4(MYH7):c.740T>G (p.Phe247Cys)

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.740T>G (p.Phe247Cys)
Other names:
p.F247C:TTC>TGC
HGVS:
  • NC_000014.9:g.23431474A>C
  • NG_007884.1:g.9188T>G
  • NM_000257.4:c.740T>GMANE SELECT
  • NP_000248.2:p.Phe247Cys
  • LRG_384t1:c.740T>G
  • LRG_384:g.9188T>G
  • NC_000014.8:g.23900683A>C
  • NM_000257.2:c.740T>G
  • NM_000257.3:c.740T>G
Protein change:
F247C
Links:
dbSNP: rs730880922
NCBI 1000 Genomes Browser:
rs730880922
Molecular consequence:
  • NM_000257.4:c.740T>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000737345Ambry Geneticscriteria provided, single submitter
Likely pathogenic
(Mar 29, 2020)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Structural basis for drug-induced allosteric changes to human β-cardiac myosin motor activity.

Winkelmann DA, Forgacs E, Miller MT, Stock AM.

Nat Commun. 2015 Aug 6;6:7974. doi: 10.1038/ncomms8974.

PubMed [citation]
PMID:
26246073
PMCID:
PMC4918383

Details of each submission

From Ambry Genetics, SCV000737345.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

The p.F247C variant (also known as c.740T>G), located in coding exon 7 of the MYH7 gene, results from a T to G substitution at nucleotide position 740. The phenylalanine at codon 247 is replaced by cysteine, an amino acid with highly dissimilar properties. Another alteration affecting the same amino acid, p.F247L (c.739T>C), has been reported in association with hypertrophic cardiomyopathy (HCM) (García-Castro M et al. Rev Esp Cardiol, 2009 Jan;62:48-56). Based on internal structural assessment, the p.F247C alteration disrupts the local structure of the myosin head at the interface between the N and C-terminal domains (Winkelmann DA et al. Nat Commun, 2015 Aug;6:7974). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Nov 27, 2021

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