U.S. flag

An official website of the United States government

NM_000257.4(MYH7):c.4321G>T (p.Ala1441Ser) AND Sudden unexplained death

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jan 16, 2019
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:
RCV000201892.9

Allele description [Variation Report for NM_000257.4(MYH7):c.4321G>T (p.Ala1441Ser)]

NM_000257.4(MYH7):c.4321G>T (p.Ala1441Ser)

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.4321G>T (p.Ala1441Ser)
HGVS:
  • NC_000014.9:g.23417535C>A
  • NG_007884.1:g.23127G>T
  • NM_000257.4:c.4321G>TMANE SELECT
  • NP_000248.2:p.Ala1441Ser
  • LRG_384t1:c.4321G>T
  • LRG_384:g.23127G>T
  • NC_000014.8:g.23886744C>A
  • NM_000257.2:c.4321G>T
  • NM_000257.3:c.4321G>T
  • NR_126491.1:n.816C>A
Protein change:
A1441S
Links:
dbSNP: rs745414245
NCBI 1000 Genomes Browser:
rs745414245
Molecular consequence:
  • NM_000257.4:c.4321G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_126491.1:n.816C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Sudden unexplained death
Identifiers:
MedGen: C0520806

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000256651Agnes Ginges Centre for Molecular Cardiology, Centenary Institute
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Jan 16, 2019) 		germlineresearch

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedresearch

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 Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, SCV000256651.3

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

Description

The MYH7 Ala1441Ser variant is located within the myosin tail region of the MYH7 gene and is observed in the Genome Aggregation Database (http://gnomad.broadinstitute.org/), at an allele frequency of 0.000021. We detected this rare variant in a sudden unexplained death case, with no signs of cardiomyopathy found on autopsy. In silico tools SIFT, MutationTaster and PolyPhen-2 predict this variant to deleterious. No reports of this variant was found in the literature. Based on the adapted ACMG criteria (Kelly MA, et al., 2018) this variant is rare in the general population (PM2), and multiple in silico tools predict this variant to have a deleterious affect (PP3), therefore we classify MYH7 Ala1441Ser as a variant of 'uncertain significance'.

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

Last Updated: Oct 26, 2024