NM_000257.4(MYH7):c.2700T>G (p.Asp900Glu) AND Hypertrophic cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 11, 2021
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:: RCV001342138.7

Allele description [Variation Report for NM_000257.4(MYH7):c.2700T>G (p.Asp900Glu)]

NM_000257.4(MYH7):c.2700T>G (p.Asp900Glu)

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.2700T>G (p.Asp900Glu)

HGVS:

NC_000014.9:g.23424129A>C
NG_007884.1:g.16533T>G
NM_000257.4:c.2700T>GMANE SELECT
NP_000248.2:p.Asp900Glu
LRG_384:g.16533T>G
NC_000014.8:g.23893338A>C

Protein change:

D900E

Links:

dbSNP: rs730880755

NCBI 1000 Genomes Browser:

rs730880755

Molecular consequence:

NM_000257.4:c.2700T>G - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001536049	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 11, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 24793961, 27532257, 31006259, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001536049

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 11, 2021)

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

Characterization of a phenotype-based genetic test prediction score for unrelated patients with hypertrophic cardiomyopathy.

Bos JM, Will ML, Gersh BJ, Kruisselbrink TM, Ommen SR, Ackerman MJ.

Mayo Clin Proc. 2014 Jun;89(6):727-37. doi: 10.1016/j.mayocp.2014.01.025. Epub 2014 May 1.

PubMed [citation]

PMID:: 24793961
PMCID:: PMC4234122

Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, Mazzarotto F, Blair E, Seller A, Taylor JC, Minikel EV, Exome Aggregation Consortium, MacArthur DG, Farrall M, Cook SA, Watkins H.

Genet Med. 2017 Feb;19(2):192-203. doi: 10.1038/gim.2016.90. Epub 2016 Aug 17.

PubMed [citation]

PMID:: 27532257
PMCID:: PMC5116235

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001536049.4

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

Description

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 is found within a region of MYH7 between codons 181 and 937 that contains the majority of the myosin head domain. Missense variants in this region have been shown to be significantly overrepresented in individuals with hypertrophic cardiomyopathy (PMID: 27532257). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This missense change has been observed in individual(s) with clinical features of hypertrophic cardiomyopathy (PMID: 24793961, 27532257, 31006259, Invitae). ClinVar contains an entry for this variant (Variation ID: 1038786). This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with glutamic acid at codon 900 of the MYH7 protein (p.Asp900Glu). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and glutamic acid.

#	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

ClinVar

Relating variation to medicine