NM_000257.4(MYH7):c.4720C>T (p.Arg1574Trp) AND not specified

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: May 24, 2021
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:: RCV000035927.7

Allele description [Variation Report for NM_000257.4(MYH7):c.4720C>T (p.Arg1574Trp)]

NM_000257.4(MYH7):c.4720C>T (p.Arg1574Trp)

Genes:

LOC126861897:BRD4-independent group 4 enhancer GRCh37_chr14:23884455-23885654 [Gene]
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.4720C>T (p.Arg1574Trp)

HGVS:

NC_000014.9:g.23416237G>A
NG_007884.1:g.24425C>T
NM_000257.4:c.4720C>TMANE SELECT
NP_000248.2:p.Arg1574Trp
LRG_384t1:c.4720C>T
LRG_384:g.24425C>T
NC_000014.8:g.23885446G>A
NM_000257.2:c.4720C>T
NM_000257.3:c.4720C>T
NR_126491.1:n.498G>A
c.4720C>T

Protein change:

R1574W

Links:

dbSNP: rs397516227

NCBI 1000 Genomes Browser:

rs397516227

Molecular consequence:

NM_000257.4:c.4720C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_126491.1:n.498G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000059578	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Jan 16, 2014)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001737819	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (May 24, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 24503780, 27532257, 28606303 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000059578

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Jan 16, 2014)

germline

clinical testing

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

SCV001737819

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(May 24, 2021)

germline

clinical testing

PubMed (3)
[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	2	2	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

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing.

Pugh TJ, Kelly MA, Gowrisankar S, Hynes E, Seidman MA, Baxter SM, Bowser M, Harrison B, Aaron D, Mahanta LM, Lakdawala NK, McDermott G, White ET, Rehm HL, Lebo M, Funke BH.

Genet Med. 2014 Aug;16(8):601-8. doi: 10.1038/gim.2013.204. Epub 2014 Feb 6.

PubMed [citation]

PMID:: 24503780

See all PubMed Citations (4)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000059578.5

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

Description

proposed classification - variant undergoing re-assessment, contact laboratory

#	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		2	not provided	2	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001737819.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: MYH7 c.4720C>T (p.Arg1574Trp) results in a non-conservative amino acid change located in the Myosin tail domain (IPR002928) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251410 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4720C>T has been reported in the literature in individuals affected with Dilated cardiomyopathy (Pugh_2014, Walsh_2017). 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. 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: Sep 29, 2024

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