NM_000257.4(MYH7):c.4283T>C (p.Leu1428Ser) AND Cardiomyopathy

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 6, 2022
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:: RCV000777946.7

Allele description [Variation Report for NM_000257.4(MYH7):c.4283T>C (p.Leu1428Ser)]

NM_000257.4(MYH7):c.4283T>C (p.Leu1428Ser)

Genes:

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.4283T>C (p.Leu1428Ser)

Other names:

p.L1428S:TTG>TCG; NM_000257.4(MYH7):c.4283T>C

HGVS:

NC_000014.9:g.23417573A>G
NG_007884.1:g.23089T>C
NM_000257.4:c.4283T>CMANE SELECT
NP_000248.2:p.Leu1428Ser
LRG_384t1:c.4283T>C
LRG_384:g.23089T>C
NC_000014.8:g.23886782A>G
NM_000257.2:c.4283T>C
NM_000257.3:c.4283T>C
NR_126491.1:n.854A>G

Protein change:

L1428S

Links:

dbSNP: rs727503244

NCBI 1000 Genomes Browser:

rs727503244

Molecular consequence:

NM_000257.4:c.4283T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_126491.1:n.854A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

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

Recent activity

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JGI_CABD1429.fwd NIH_XGC_tropLun1 Xenopus tropicalis cDNA clone IMAGE:7807200 5'...
JGI_CABD1429.fwd NIH_XGC_tropLun1 Xenopus tropicalis cDNA clone IMAGE:7807200 5', mRNA sequence
gi|59652660|gnl|dbEST|27784917|gb|D 92.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000914044	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Dec 6, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 20818890, 26914223, 27532257, 33495597, 25741868
SCV003838101	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 7, 2022)	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

SCV000914044

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Dec 6, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV003838101

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

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 7, 2022)

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

Myocardial fibrosis as an early manifestation of hypertrophic cardiomyopathy.

Ho CY, López B, Coelho-Filho OR, Lakdawala NK, Cirino AL, Jarolim P, Kwong R, González A, Colan SD, Seidman JG, Díez J, Seidman CE.

N Engl J Med. 2010 Aug 5;363(6):552-63. doi: 10.1056/NEJMoa1002659.

PubMed [citation]

PMID:: 20818890
PMCID:: PMC3049917

Evaluation of the Mayo Clinic Phenotype-Based Genotype Predictor Score in Patients with Clinically Diagnosed Hypertrophic Cardiomyopathy.

Murphy SL, Anderson JH, Kapplinger JD, Kruisselbrink TM, Gersh BJ, Ommen SR, Ackerman MJ, Bos JM.

J Cardiovasc Transl Res. 2016 Apr;9(2):153-61. doi: 10.1007/s12265-016-9681-5. Epub 2016 Feb 25.

PubMed [citation]

PMID:: 26914223
PMCID:: PMC4907543

See all PubMed Citations (5)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000914044.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This missense variant replaces leucine with serine at codon 1428 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 three individuals affected with hypertrophic cardiomyopathy (PMID: 20818890, 26914223, 27532257, 33495597). This variant has been identified in 12/282834 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 CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario, SCV003838101.1

#	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: Sep 29, 2024

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