NM_000257.4(MYH7):c.4823G>A (p.Arg1608His) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (4 submissions)
Last evaluated:: May 1, 2023
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:: RCV001751594.12

Allele description

NM_000257.4(MYH7):c.4823G>A (p.Arg1608His)

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.4823G>A (p.Arg1608His)

HGVS:

NC_000014.9:g.23416134C>T
NG_007884.1:g.24528G>A
NM_000257.4:c.4823G>AMANE SELECT
NP_000248.2:p.Arg1608His
LRG_384t1:c.4823G>A
LRG_384:g.24528G>A
NC_000014.8:g.23885343C>T
NM_000257.2:c.4823G>A
NM_000257.3:c.4823G>A
NR_126491.1:n.395C>T

Protein change:

R1608H

Links:

dbSNP: rs587779391

NCBI 1000 Genomes Browser:

rs587779391

Molecular consequence:

NM_000257.4:c.4823G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_126491.1:n.395C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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ENSLAFG00000026180 AND (alive[prop]) (0)
Gene
ENSTBEG00000013828 AND (alive[prop]) (0)
Gene
forkhead box protein N3 [Takifugu rubripes]
forkhead box protein N3 [Takifugu rubripes]
gi|1698291194|ref|XP_003971527.2|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002007755	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Feb 17, 2020)	germline	clinical testing	Citation Link,
SCV002502288	AiLife Diagnostics, AiLife Diagnostics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Aug 31, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004129085	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (May 1, 2023)	germline	clinical testing	Citation Link,
SCV004848556	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Apr 14, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24664454, 25741868

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	2	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

Novel mutations widen the phenotypic spectrum of slow skeletal/β-cardiac myosin (MYH7) distal myopathy.

Lamont PJ, Wallefeld W, Hilton-Jones D, Udd B, Argov Z, Barboi AC, Bonneman C, Boycott KM, Bushby K, Connolly AM, Davies N, Beggs AH, Cox GF, Dastgir J, DeChene ET, Gooding R, Jungbluth H, Muelas N, Palmio J, Penttilä S, Schmedding E, Suominen T, et al.

Hum Mutat. 2014 Jul;35(7):868-79. doi: 10.1002/humu.22553. Epub 2014 May 21.

PubMed [citation]

PMID:: 24664454
PMCID:: PMC4112555

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneDx, SCV002007755.2

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

Description

Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function

#	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 AiLife Diagnostics, AiLife Diagnostics, SCV002502288.1

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

#	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		1	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV004129085.8

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

Description

MYH7: PM2, PP2, PP3, PS4:Supporting

#	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		1	not provided	not provided	not provided

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004848556.1

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

Description

The p.Arg1608His variant in MYH7 has not been previously reported in individuals with cardiomyopathy but has been identified in 0.006% (1/16252) of African chromosomes and in 0.004% (1/21648) of Finnish chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting.

#	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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