NM_000257.4(MYH7):c.11C>T (p.Ser4Leu) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 13, 2023
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:: RCV004022330.1

Allele description [Variation Report for NM_000257.4(MYH7):c.11C>T (p.Ser4Leu)]

NM_000257.4(MYH7):c.11C>T (p.Ser4Leu)

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.11C>T (p.Ser4Leu)

HGVS:

NC_000014.9:g.23433722G>A
NG_007884.1:g.6940C>T
NM_000257.4:c.11C>TMANE SELECT
NP_000248.2:p.Ser4Leu
LRG_384t1:c.11C>T
LRG_384:g.6940C>T
NC_000014.8:g.23902931G>A
NM_000257.2:c.11C>T
NM_000257.3:c.11C>T

Protein change:

S4L

Links:

dbSNP: rs758659692

NCBI 1000 Genomes Browser:

rs758659692

Molecular consequence:

NM_000257.4:c.11C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005033779	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Nov 13, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 22765922, 24510615, 25342278, 27247418, 28356264, 29773157, 34542152 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005033779

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Nov 13, 2023)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Resequencing the whole MYH7 gene (including the intronic, promoter, and 3' UTR sequences) in hypertrophic cardiomyopathy.

Coto E, Reguero JR, Palacín M, Gómez J, Alonso B, Iglesias S, Martín M, Tavira B, Díaz-Molina B, Morales C, Morís C, Rodríguez-Lambert JL, Corao AI, Díaz M, Alvarez V.

J Mol Diagn. 2012 Sep;14(5):518-24. doi: 10.1016/j.jmoldx.2012.04.001. Epub 2012 Jul 2.

PubMed [citation]

PMID:: 22765922

Distinguishing hypertrophic cardiomyopathy-associated mutations from background genetic noise.

Kapplinger JD, Landstrom AP, Bos JM, Salisbury BA, Callis TE, Ackerman MJ.

J Cardiovasc Transl Res. 2014 Apr;7(3):347-61. doi: 10.1007/s12265-014-9542-z. Epub 2014 Feb 8.

PubMed [citation]

PMID:: 24510615
PMCID:: PMC4849132

See all PubMed Citations (7)

Details of each submission

From Ambry Genetics, SCV005033779.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

The p.S4L variant (also known as c.11C>T), located in coding exon 1 of the MYH7 gene, results from a C to T substitution at nucleotide position 11. The serine at codon 4 is replaced by leucine, an amino acid with dissimilar properties. This alteration has been reported in cardiomyopathy cohorts (Coto E et al. J Mol Diagn, 2012 Sep;14:518-24; Gómez J et al. Circ Cardiovasc Genet, 2017 Apr;10:; Ware JS et al. J Am Coll Cardiol, 2018 May;71:2293-2302). This alteration has also been reported in ostensibly healthy individuals (Kapplinger JD et al. J Cardiovasc Transl Res, 2014 Apr;7:347-61; Homburger JR et al. Proc Natl Acad Sci U S A, 2016 Jun;113:6701-6; Park J et al. Hum Mol Genet, 2022 Mar;31:827-837). This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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

Last Updated: May 7, 2024

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