NM_000257.4(MYH7):c.4076G>A (p.Arg1359His) AND Cardiomyopathy

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Nov 30, 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:: RCV001171201.9

Allele description [Variation Report for NM_000257.4(MYH7):c.4076G>A (p.Arg1359His)]

NM_000257.4(MYH7):c.4076G>A (p.Arg1359His)

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.4076G>A (p.Arg1359His)

HGVS:

NC_000014.9:g.23418303C>T
NG_007884.1:g.22359G>A
NM_000257.4:c.4076G>AMANE SELECT
NP_000248.2:p.Arg1359His
LRG_384t1:c.4076G>A
LRG_384:g.22359G>A
NC_000014.8:g.23887512C>T
NM_000257.2:c.4076G>A
NM_000257.3:c.4076G>A

Protein change:

R1359H

Links:

dbSNP: rs750836033

NCBI 1000 Genomes Browser:

rs750836033

Molecular consequence:

NM_000257.4:c.4076G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001333898	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 16, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001347682	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Dec 9, 2022)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 1218377, 26468400, 29447731, 31983221, 34036930, 34983622, 25741868
SCV004823184	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Nov 30, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 26468400, 29447731, 31983221, 34036930, 34983622, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001333898

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

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 16, 2020)

germline

clinical testing

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

SCV001347682

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Dec 9, 2022)

germline

clinical testing

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

SCV004823184

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Nov 30, 2023)

germline

clinical testing

PubMed (6)
[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	4	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

A process model of repetition in aphasia: an investigation of phonological and morphological interactions in aphasic error performance.

Martin AD, Wasserman NH, Gilden L, Gerstman L, West JA.

Brain Lang. 1975 Oct;2(4):434-50. No abstract available.

PubMed [citation]

PMID:: 1218377

Results of comprehensive diagnostic work-up in 'idiopathic' dilated cardiomyopathy.

Broch K, Andreassen AK, Hopp E, Leren TP, Scott H, Müller F, Aakhus S, Gullestad L.

Open Heart. 2015;2(1):e000271. doi: 10.1136/openhrt-2015-000271.

PubMed [citation]

PMID:: 26468400
PMCID:: PMC4600247

See all PubMed Citations (7)

Details of each submission

From CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario, SCV001333898.2

#	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

From Color Diagnostics, LLC DBA Color Health, SCV001347682.3

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

Description

This missense variant replaces arginine with histidine at codon 1359 of the MYH7 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in five unrelated individuals affected with dilated cardiomyopathy (PMID: 26468400, 31983221, 34036930) or noncompaction cardiomyopathy (PMID: 29447731, ClinVar SCV001218377.3). This variant has also been observed in a fetus with congenital heart defects (PMID: 34983622). This variant has been identified in 5/251432 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#	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 All of Us Research Program, National Institutes of Health, SCV004823184.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	not provided	not provided	clinical testing	PubMed (6)

Description

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	108544	not provided	not provided		4	not provided	not provided	not provided

Last Updated: Oct 13, 2024

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