NM_000257.4(MYH7):c.3551A>T (p.Gln1184Leu) AND not specified

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Feb 15, 2023
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:: RCV000223885.3

Allele description [Variation Report for NM_000257.4(MYH7):c.3551A>T (p.Gln1184Leu)]

NM_000257.4(MYH7):c.3551A>T (p.Gln1184Leu)

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.3551A>T (p.Gln1184Leu)

Other names:

p.Q1184L:CAG>CTG

HGVS:

NC_000014.9:g.23420020T>A
NG_007884.1:g.20642A>T
NM_000257.4:c.3551A>TMANE SELECT
NP_000248.2:p.Gln1184Leu
LRG_384t1:c.3551A>T
LRG_384:g.20642A>T
NC_000014.8:g.23889229T>A
NM_000257.2:c.3551A>T
NM_000257.3:c.3551A>T

Protein change:

Q1184L

Links:

dbSNP: rs546586969

NCBI 1000 Genomes Browser:

rs546586969

Molecular consequence:

NM_000257.4:c.3551A>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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
SCV000280340	Stanford Center for Inherited Cardiovascular Disease, Stanford University	no assertion criteria provided	Uncertain significance (Mar 3, 2014)	germline	clinical testing
SCV003844758	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Feb 15, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30297972, 31308319 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000280340

Stanford Center for Inherited Cardiovascular Disease, Stanford University

no assertion criteria provided

Uncertain significance
(Mar 3, 2014)

germline

clinical testing

SCV003844758

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Feb 15, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genotype and Lifetime Burden of Disease in Hypertrophic Cardiomyopathy: Insights from the Sarcomeric Human Cardiomyopathy Registry (SHaRe).

Ho CY, Day SM, Ashley EA, Michels M, Pereira AC, Jacoby D, Cirino AL, Fox JC, Lakdawala NK, Ware JS, Caleshu CA, Helms AS, Colan SD, Girolami F, Cecchi F, Seidman CE, Sajeev G, Signorovitch J, Green EM, Olivotto I.

Circulation. 2018 Oct 2;138(14):1387-1398. doi: 10.1161/CIRCULATIONAHA.117.033200. Epub 2018 Aug 23.

PubMed [citation]

PMID:: 30297972
PMCID:: PMC6170149

Presence of Hypertrophic Cardiomyopathy Related Gene Mutations and Clinical Manifestations in Vietnamese Patients With Hypertrophic Cardiomyopathy.

Tran Vu MT, Nguyen TV, Huynh NV, Nguyen Thai HT, Pham Nguyen V, Ho Huynh TD.

Circ J. 2019 Aug 23;83(9):1908-1916. doi: 10.1253/circj.CJ-19-0190. Epub 2019 Jul 12.

PubMed [citation]

PMID:: 31308319

Details of each submission

From Stanford Center for Inherited Cardiovascular Disease, Stanford University, SCV000280340.1

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

Description

Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. p.Gln1184Leu in the MYH7 gene at exon 27. This variant is novel and has not been reported as a disease-causing mutation or as a benign polymorphism. This is a non-conserved amino acid substitution which changes an uncharged polar glutamine to a nonpolar leucine residue. In silico analysis with PolyPhen-2 predicts the variant to be possibly damaging with a score of 0.689. Mutation Taster predicts this change to be damaging with a score of 113. The Glutamine at codon 1184 is conserved across species, as are neighboring amino acids. A variant at codon 1193 (p.Arg1193His) has been reported in HGMD in association with cardiomyopathy (Stendon P et al., 2009). In total the variant has not been seen in ~6000 individuals from publicly available population datasets. There is no variation at codon 1184 listed in the NHLBI Exome Sequencing Project dataset, which currently includes variant calls on ~6000 Caucasian and African American individuals (as of 5/31/13). Note that this dataset does not match the patient's ancestry. There is also no variation at this codon listed in dbSNP or 1000 genomes (as of 5/31/13).

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003844758.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: MYH7 c.3551A>T (p.Gln1184Leu) results in a non-conservative amino acid change located in the Myosin tail domain (IPR002928) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.6e-05 in 215646 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in MYH7 causing Cardiomyopathy (4.6e-05 vs 0.0013), allowing no conclusion about variant significance. c.3551A>T has been reported in the literature in individuals affected with hypertrophic cardiomyopathy, while it was also identified in two asymptomatic family members related to one of the affected individuals (e.g., Ho_2018, Tran-Vu_2019). These reports do not provide unequivocal conclusions about association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 with conflicting assessments; two laboratories classified the variant as uncertain significance and one laboratory classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as 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

Last Updated: May 7, 2024

ClinVar

Relating variation to medicine