NM_000257.4(MYH7):c.2389G>A (p.Ala797Thr) AND Cardiomyopathy

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Apr 20, 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:: RCV001189214.7

Allele description [Variation Report for NM_000257.4(MYH7):c.2389G>A (p.Ala797Thr)]

NM_000257.4(MYH7):c.2389G>A (p.Ala797Thr)

Genes:

LOC126861898:BRD4-independent group 4 enhancer GRCh37_chr14:23893609-23894808 [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.2389G>A (p.Ala797Thr)

HGVS:

NC_000014.9:g.23425316C>T
NG_007884.1:g.15346G>A
NM_000257.4:c.2389G>AMANE SELECT
NP_000248.2:p.Ala797Thr
LRG_384t1:c.2389G>A
LRG_384:g.15346G>A
NC_000014.8:g.23894525C>T
NM_000257.2:c.2389G>A
NM_000257.3:c.2389G>A
P12883:p.Ala797Thr
c.2389G>A

Protein change:

A797T

Links:

UniProtKB: P12883#VAR_004591; dbSNP: rs3218716

NCBI 1000 Genomes Browser:

rs3218716

Molecular consequence:

NM_000257.4:c.2389G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiomyopathy (CMYO)
Synonyms:: Cardiomyopathies
Identifiers:: MONDO: MONDO:0004994; MedGen: C0878544; Human Phenotype Ontology: HP:0001638

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Homo sapiens long intergenic non-protein coding RNA 2932 (LINC02932), transcript...
Homo sapiens long intergenic non-protein coding RNA 2932 (LINC02932), transcript variant 6, long non-coding RNA
gi|2428898232|ref|NR_183371.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001356459	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 20, 2023)	germline	clinical testing	PubMed (26) [See all records that cite these PMIDs] 7581410, 10521296, 11186938, 11447480, 15358028, 16858239, 17125710, 20031618, 22857948, 23233322, 23283745, 24093860, 24111713, 24793961, 26969327, 27247418, 27532257, 27737317, 27831900, 27841901, 28138913, 28615295, 28790153, 33297573, 33673806, 25741868
SCV002042271	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 12, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001356459

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 20, 2023)

germline

clinical testing

PubMed (26)
[See all records that cite these PMIDs]

SCV002042271

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 12, 2020)

germline

clinical testing

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

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

Identification of a novel Ala797Thr mutation in exon 21 of the beta-myosin heavy chain gene in hypertrophic cardiomyopathy.

Moolman JC, Brink PA, Corfield VA.

Hum Mutat. 1995;6(2):197-8. No abstract available.

PubMed [citation]

PMID:: 7581410

The origins of hypertrophic cardiomyopathy-causing mutations in two South African subpopulations: a unique profile of both independent and founder events.

Moolman-Smook JC, De Lange WJ, Bruwer EC, Brink PA, Corfield VA.

Am J Hum Genet. 1999 Nov;65(5):1308-20.

PubMed [citation]

PMID:: 10521296
PMCID:: PMC1288283

See all PubMed Citations (26)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001356459.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (26)

Description

This missense variant replaces alanine with threonine at codon 797 in the myosin head/motor domain of the MYH7 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in many individuals affected with hypertrophic cardiomyopathy (PMID: 7581410, 10521296, 11186938, 11447480, 15358028, 16858239, 17125710, 20031618, 22857948, 23233322, 23283745, 24093860, 24111713, 24793961, 26969327, 27247418, 27532257, 27737317, 27831900, 28138913, 28615295, 28790153, 33297573, 33673806) and has been shown to segregate with disease in several families (PMID: 11186938, 17125710). This variant is particularly common in the South African individuals affected with hypertrophic cardiomyopathy (PMID: 27841901). This variant has been identified in 6/251468 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic.

#	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

From CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario, SCV002042271.1

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

#	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: Jun 2, 2024

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