NM_000257.4(MYH7):c.4646C>A (p.Ala1549Asp) AND Hypertrophic cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 24, 2023
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:: RCV003586534.2

Allele description [Variation Report for NM_000257.4(MYH7):c.4646C>A (p.Ala1549Asp)]

NM_000257.4(MYH7):c.4646C>A (p.Ala1549Asp)

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.4646C>A (p.Ala1549Asp)

HGVS:

NC_000014.9:g.23416311G>T
NG_007884.1:g.24351C>A
NG_086395.1:g.1166G>T
NM_000257.4:c.4646C>AMANE SELECT
NM_001407004.1:c.4646C>A
NP_000248.2:p.Ala1549Asp
NP_000248.2:p.Ala1549Asp
NP_001393933.1:p.Ala1549Asp
LRG_384t1:c.4646C>A
LRG_384:g.24351C>A
LRG_384p1:p.Ala1549Asp
NC_000014.8:g.23885520G>T
NM_000257.2:c.4646C>A

Protein change:

A1549D

Molecular consequence:

NM_000257.4:c.4646C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407004.1:c.4646C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hypertrophic cardiomyopathy
Synonyms:: HYPERTROPHIC MYOCARDIOPATHY
Identifiers:: MONDO: MONDO:0005045; MeSH: D002312; MedGen: C0007194; Human Phenotype Ontology: HP:0001639

Recent activity

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Chaenomeles sinensis voucher 12157 ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit (rbcL) gene, partial cds; chloroplast
gi|379062334|gb|JQ391400.1|

Nucleotide
PREDICTED: Cucumis sativus flowering locus K homology domain (LOC101206130), tra...
PREDICTED: Cucumis sativus flowering locus K homology domain (LOC101206130), transcript variant X1, mRNA
gi|1784859785|ref|XM_004139200.3|

Nucleotide
glycerol dehydrogenase [Klebsiella variicola]
glycerol dehydrogenase [Klebsiella variicola]
gi|635939951|gb|KDH20221.1||gnl|WGS |AE36_05114T0

Protein
Related Structures (List) for Protein (Select 1706694) (34)
Structure
Nucleotide Links for Protein (Select 11545863) (6)
Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004249551	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 24, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004249551

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 24, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004249551.1

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

Description

This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 1549 of the MYH7 protein (p.Ala1549Asp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of 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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