NM_000257.4(MYH7):c.4663G>C (p.Glu1555Gln) AND Hypertrophic cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 5, 2020
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:: RCV001306103.7

Allele description [Variation Report for NM_000257.4(MYH7):c.4663G>C (p.Glu1555Gln)]

NM_000257.4(MYH7):c.4663G>C (p.Glu1555Gln)

Genes:

LOC126861897:BRD4-independent group 4 enhancer GRCh37_chr14:23884455-23885654 [Gene]
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.4663G>C (p.Glu1555Gln)

HGVS:

NC_000014.9:g.23416294C>G
NG_007884.1:g.24368G>C
NM_000257.4:c.4663G>CMANE SELECT
NP_000248.2:p.Glu1555Gln
LRG_384t1:c.4663G>C
LRG_384:g.24368G>C
NC_000014.8:g.23885503C>G
NM_000257.2:c.4663G>C
NR_126491.1:n.555C>G

Protein change:

E1555Q

Links:

dbSNP: rs727505176

NCBI 1000 Genomes Browser:

rs727505176

Molecular consequence:

NM_000257.4:c.4663G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_126491.1:n.555C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001495460	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 5, 2020)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 23782526, 31130376, 22765922, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001495460

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 5, 2020)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

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

Somatic MYH7, MYBPC3, TPM1, TNNT2 and TNNI3 mutations in sporadic hypertrophic cardiomyopathy.

Núñez L, Gimeno-Blanes JR, Rodríguez-García MI, Monserrat L, Zorio E, Coats C, McGregor CG, Hernandez del Rincón JP, Castro-Beiras A, Hermida-Prieto M.

Circ J. 2013;77(9):2358-65. Epub 2013 Jun 19.

PubMed [citation]

PMID:: 23782526

Recessive MYH7-related myopathy in two families.

Beecroft SJ, van de Locht M, de Winter JM, Ottenheijm CA, Sewry CA, Mohammed S, Ryan MM, Woodcock IR, Sanders L, Gooding R, Davis MR, Oates EC, Laing NG, Ravenscroft G, McLean CA, Jungbluth H.

Neuromuscul Disord. 2019 Jun;29(6):456-467. doi: 10.1016/j.nmd.2019.04.002. Epub 2019 Apr 12.

PubMed [citation]

PMID:: 31130376

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001495460.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with glutamine at codon 1555 of the MYH7 protein (p.Glu1555Gln). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and glutamine. This variant has not been reported in the literature in individuals with MYH7-related conditions. ClinVar contains an entry for this variant (Variation ID: 179858). 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. This variant disrupts the p.Glu1555 amino acid residue in MYH7. Other variant(s) that disrupt this residue have been observed in individuals with MYH7-related conditions (PMID: 23782526, 31130376, 22765922), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0").

#	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: Sep 29, 2024

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