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NM_000257.4(MYH7):c.4240C>A (p.Leu1414Met) AND Hypertrophic cardiomyopathy

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
May 22, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000171840.11

Allele description [Variation Report for NM_000257.4(MYH7):c.4240C>A (p.Leu1414Met)]

NM_000257.4(MYH7):c.4240C>A (p.Leu1414Met)

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.4240C>A (p.Leu1414Met)
HGVS:
  • NC_000014.9:g.23417616G>T
  • NG_007884.1:g.23046C>A
  • NM_000257.4:c.4240C>AMANE SELECT
  • NP_000248.2:p.Leu1414Met
  • LRG_384t1:c.4240C>A
  • LRG_384:g.23046C>A
  • NC_000014.8:g.23886825G>T
  • NM_000257.2:c.4240C>A
  • NM_000257.3:c.4240C>A
  • P12883:p.Leu1414Met
Protein change:
L1414M
Links:
UniProtKB: P12883#VAR_045928; dbSNP: rs201895208
NCBI 1000 Genomes Browser:
rs201895208
Molecular consequence:
  • NM_000257.4:c.4240C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hypertrophic cardiomyopathy
Synonyms:
HYPERTROPHIC MYOCARDIOPATHY
Identifiers:
MONDO: MONDO:0005045; MeSH: D002312; MedGen: C0007194; Human Phenotype Ontology: HP:0001639

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000050864Biesecker Lab/Clinical Genomics Section, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Apr 5, 2018) 		unknownresearch

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

SCV001233871Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(May 22, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownno1not 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

Shared genetic causes of cardiac hypertrophy in children and adults.

Morita H, Rehm HL, Menesses A, McDonough B, Roberts AE, Kucherlapati R, Towbin JA, Seidman JG, Seidman CE.

N Engl J Med. 2008 May 1;358(18):1899-908. doi: 10.1056/NEJMoa075463. Epub 2008 Apr 9.

PubMed [citation]
PMID:
18403758
PMCID:
PMC2752150
See all PubMed Citations (3)

Details of each submission

From Biesecker Lab/Clinical Genomics Section, National Institutes of Health, SCV000050864.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedresearch PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownnonot providednot providednot provided1not providednot providednot provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001233871.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1414 of the MYH7 protein (p.Leu1414Met). This variant is not present in population databases (gnomAD no frequency). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYH7 protein function. ClinVar contains an entry for this variant (Variation ID: 191579). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 18403758). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Sep 29, 2024