NM_000257.4(MYH7):c.2206A>G (p.Ile736Val) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Nov 23, 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:: RCV000225741.7

Allele description [Variation Report for NM_000257.4(MYH7):c.2206A>G (p.Ile736Val)]

NM_000257.4(MYH7):c.2206A>G (p.Ile736Val)

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.2206A>G (p.Ile736Val)

HGVS:

NC_000014.9:g.23425775T>C
NG_007884.1:g.14887A>G
NM_000257.4:c.2206A>GMANE SELECT
NP_000248.2:p.Ile736Val
LRG_384t1:c.2206A>G
LRG_384:g.14887A>G
NC_000014.8:g.23894984T>C
NM_000257.2:c.2206A>G
NM_000257.3:c.2206A>G
c.2206A>G

Protein change:

I736V

Links:

dbSNP: rs397516138

NCBI 1000 Genomes Browser:

rs397516138

Molecular consequence:

NM_000257.4:c.2206A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000208454	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jan 31, 2020)	germline	clinical testing	Citation Link,
SCV000927919	Blueprint Genetics	criteria provided, single submitter (Blueprint Genetics Variant Classification Scheme)	Uncertain significance (Sep 6, 2018)	germline	clinical testing	Citation Link,
SCV004226503	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 23, 2022)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 24793961, 25611685, 27247418, 27532257, 32894683, 34542152, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000208454

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Jan 31, 2020)

germline

clinical testing

Citation Link,

SCV000927919

Blueprint Genetics

criteria provided, single submitter

(Blueprint Genetics Variant Classification Scheme)

Uncertain significance
(Sep 6, 2018)

germline

clinical testing

Citation Link,

SCV004226503

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 23, 2022)

germline

clinical testing

PubMed (7)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Characterization of a phenotype-based genetic test prediction score for unrelated patients with hypertrophic cardiomyopathy.

Bos JM, Will ML, Gersh BJ, Kruisselbrink TM, Ommen SR, Ackerman MJ.

Mayo Clin Proc. 2014 Jun;89(6):727-37. doi: 10.1016/j.mayocp.2014.01.025. Epub 2014 May 1.

PubMed [citation]

PMID:: 24793961
PMCID:: PMC4234122

Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity.

Alfares AA, Kelly MA, McDermott G, Funke BH, Lebo MS, Baxter SB, Shen J, McLaughlin HM, Clark EH, Babb LJ, Cox SW, DePalma SR, Ho CY, Seidman JG, Seidman CE, Rehm HL.

Genet Med. 2015 Nov;17(11):880-8. doi: 10.1038/gim.2014.205. Epub 2015 Jan 22. Erratum in: Genet Med. 2015 Apr;17(4):319.

PubMed [citation]

PMID:: 25611685

See all PubMed Citations (7)

Details of each submission

From GeneDx, SCV000208454.13

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

Description

Identified in patient's with hypertrophic cardiomyopathy in published literature, although detailed clinical information was not provided (Bos et al., 2014; Walsh et al., 2017; Alfares et al., 2015; Homburger et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); A different missense change at this residue (I736T) has been reported as pathogenic in the published literature in association with hypertrophic cardiomyopathy (Erdmann J et al., 2003; Mohiddin S et al., 2003; Ingles J et al., 2005; Perrot A et al., 2005); This variant is associated with the following publications: (PMID: 27247418, 27532257, 24793961, 25611685)

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

From Blueprint Genetics, SCV000927919.1

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

#	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 Mayo Clinic Laboratories, Mayo Clinic, SCV004226503.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (7)

Description

PM1, PM2_supporting, PM5

#	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		1	not provided	not provided	not provided

Last Updated: May 7, 2024

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