NM_000257.4(MYH7):c.3856G>A (p.Glu1286Lys) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 19, 2020
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:: RCV000035871.7

Allele description [Variation Report for NM_000257.4(MYH7):c.3856G>A (p.Glu1286Lys)]

NM_000257.4(MYH7):c.3856G>A (p.Glu1286Lys)

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.3856G>A (p.Glu1286Lys)

HGVS:

NC_000014.9:g.23419293C>T
NG_007884.1:g.21369G>A
NM_000257.4:c.3856G>AMANE SELECT
NP_000248.2:p.Glu1286Lys
LRG_384t1:c.3856G>A
LRG_384:g.21369G>A
NC_000014.8:g.23888502C>T
NM_000257.2:c.3856G>A
NM_000257.3:c.3856G>A
c.3856G>A

Protein change:

E1286K

Links:

dbSNP: rs397516196

NCBI 1000 Genomes Browser:

rs397516196

Molecular consequence:

NM_000257.4:c.3856G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000059522	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Apr 19, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22464770, 27532257, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000059522

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Apr 19, 2020)

germline

clinical testing

PubMed (3)
[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	5	2	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genetic testing for dilated cardiomyopathy in clinical practice.

Lakdawala NK, Funke BH, Baxter S, Cirino AL, Roberts AE, Judge DP, Johnson N, Mendelsohn NJ, Morel C, Care M, Chung WK, Jones C, Psychogios A, Duffy E, Rehm HL, White E, Seidman JG, Seidman CE, Ho CY.

J Card Fail. 2012 Apr;18(4):296-303. doi: 10.1016/j.cardfail.2012.01.013. Epub 2012 Feb 15.

PubMed [citation]

PMID:: 22464770
PMCID:: PMC3666099

Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, Mazzarotto F, Blair E, Seller A, Taylor JC, Minikel EV, Exome Aggregation Consortium, MacArthur DG, Farrall M, Cook SA, Watkins H.

Genet Med. 2017 Feb;19(2):192-203. doi: 10.1038/gim.2016.90. Epub 2016 Aug 17.

PubMed [citation]

PMID:: 27532257
PMCID:: PMC5116235

See all PubMed Citations (3)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000059522.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	5	not provided	not provided	clinical testing	PubMed (3)

Description

The Glu1286Lys variant in MYH7 has been reported in two young children with dilated cardiomyopathy (DCM), one of whom carried another variant that likely contributed to disease severity (Lakdawala 2012 PMID:22464770, Walsh 2017 PMID:27532257, LMM data). This variant has also been reported by another clinical laboratory in ClinVar (Variation ID: 42978) and has been identified in 0.003% (3/113766) of European chromosomes in gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PS4_Supporting, PM2, PP3.

#	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		5	not provided	2	not provided

Last Updated: Sep 29, 2024

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