NM_000257.4(MYH7):c.4078G>A (p.Val1360Ile) AND not specified

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 12, 2019
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:: RCV000035885.8

Allele description [Variation Report for NM_000257.4(MYH7):c.4078G>A (p.Val1360Ile)]

NM_000257.4(MYH7):c.4078G>A (p.Val1360Ile)

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.4078G>A (p.Val1360Ile)

HGVS:

NC_000014.9:g.23418301C>T
NG_007884.1:g.22361G>A
NM_000257.4:c.4078G>AMANE SELECT
NP_000248.2:p.Val1360Ile
LRG_384t1:c.4078G>A
LRG_384:g.22361G>A
NC_000014.8:g.23887510C>T
NM_000257.2:c.4078G>A
NM_000257.3:c.4078G>A
c.4078G>A

Protein change:

V1360I

Links:

dbSNP: rs373231077

NCBI 1000 Genomes Browser:

rs373231077

Molecular consequence:

NM_000257.4:c.4078G>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
SCV000059536	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Aug 12, 2019)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 25132132, 27532257, 27247418, 24033266
SCV000280346	Stanford Center for Inherited Cardiovascular Disease, Stanford University	no assertion criteria provided	Uncertain significance (Jan 31, 2014)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000059536

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Aug 12, 2019)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV000280346

Stanford Center for Inherited Cardiovascular Disease, Stanford University

no assertion criteria provided

Uncertain significance
(Jan 31, 2014)

germline

clinical testing

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	2	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Malignant effects of multiple rare variants in sarcomere genes on the prognosis of patients with hypertrophic cardiomyopathy.

Wang J, Wang Y, Zou Y, Sun K, Wang Z, Ding H, Yuan J, Wei W, Hou Q, Wang H, Liu X, Zhang H, Ji Y, Zhou X, Sharma RK, Wang D, Ahmad F, Hui R, Song L.

Eur J Heart Fail. 2014 Sep;16(9):950-7. doi: 10.1002/ejhf.144. Epub 2014 Jul 31.

PubMed [citation]

PMID:: 25132132

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 (4)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000059536.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (4)

Description

Variant classified as Uncertain Significance - Favor Benign. The p.Val1360Ile variant in MYH7 has been identified in 4 individuals with HCM (Wang 2014, Homburger 2016, LMM data). It has also been identified in 8/129146 European chromosomes by gnomAD and reported in ClinVar (Variation ID #42991). Computational prediction tools and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: BP4.

#	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		2	not provided	1	not provided

From Stanford Center for Inherited Cardiovascular Disease, Stanford University, SCV000280346.1

#	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.Val1360Ile (c.4078G>A) in MYH7 This is a novel variant. We classify it as a variant of uncertain significance This variant has not been described in published literature to date (as of October 2nd, 2012). Conservation analysis indicates that Valine is not highly conserved at position 1360 across species and isoforms. In total the variant has been seen in 1/6577 published controls and publicly available population datasets. The variant was recently reported online in 1 of ~4300 Caucasian individuals and 0 of 2203 African-American individuals in the NHLBI Exome Sequencing Project dataset (as of October 2nd, 2012). The phenotype of that individuals is not publicly available, however the cohorts that were merged to create this dataset were all either general population samples or samples recruited for common cardiovascular disease such as hypertension. Note that other very likely disease causing sarcomere variants have been seen in this sample at this frequency. GeneDx reports the variant is absent in 274 presumably healthy individuals.

#	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

Last Updated: Nov 3, 2024

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