NM_002471.4(MYH6):c.4828C>T (p.Arg1610Cys) AND Hypertrophic cardiomyopathy 14

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 11, 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:: RCV000468191.6

Allele description [Variation Report for NM_002471.4(MYH6):c.4828C>T (p.Arg1610Cys)]

NM_002471.4(MYH6):c.4828C>T (p.Arg1610Cys)

Genes:

LOC126861896:BRD4-independent group 4 enhancer GRCh37_chr14:23854904-23856103 [Gene]
MYH6:myosin heavy chain 6 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q11.2

Genomic location:

Preferred name:

NM_002471.4(MYH6):c.4828C>T (p.Arg1610Cys)

HGVS:

NC_000014.9:g.23386446G>A
NG_023444.1:g.26832C>T
NM_002471.4:c.4828C>TMANE SELECT
NP_002462.2:p.Arg1610Cys
NP_002462.2:p.Arg1610Cys
LRG_389t1:c.4828C>T
LRG_389:g.26832C>T
LRG_389p1:p.Arg1610Cys
NC_000014.8:g.23855655G>A
NM_002471.3:c.4828C>T

Protein change:

R1610C

Links:

dbSNP: rs780726611

NCBI 1000 Genomes Browser:

rs780726611

Molecular consequence:

NM_002471.4:c.4828C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hypertrophic cardiomyopathy 14
Synonyms:: Familial hypertrophic cardiomyopathy 14
Identifiers:: MONDO: MONDO:0013197; MedGen: C2750467; OMIM: 613251

Recent activity

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SRX328566 (1)
SRA
Slc35a2 solute carrier family 35 (UDP-galactose transporter), member A2 [Mus mus...
Slc35a2 solute carrier family 35 (UDP-galactose transporter), member A2 [Mus musculus]
Gene ID:22232

Gene
22232[uid] AND (alive[prop]) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000546139	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 11, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 28991257, 30471092, 32746448, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000546139

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 11, 2023)

germline

clinical testing

PubMed (4)
[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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands.

Jin SC, Homsy J, Zaidi S, Lu Q, Morton S, DePalma SR, Zeng X, Qi H, Chang W, Sierant MC, Hung WC, Haider S, Zhang J, Knight J, Bjornson RD, Castaldi C, Tikhonoa IR, Bilguvar K, Mane SM, Sanders SJ, Mital S, Russell MW, et al.

Nat Genet. 2017 Nov;49(11):1593-1601. doi: 10.1038/ng.3970. Epub 2017 Oct 9.

PubMed [citation]

PMID:: 28991257
PMCID:: PMC5675000

Targeted panel sequencing in adult patients with left ventricular non-compaction reveals a large genetic heterogeneity.

Richard P, Ader F, Roux M, Donal E, Eicher JC, Aoutil N, Huttin O, Selton-Suty C, Coisne D, Jondeau G, Damy T, Mansencal N, Casalta AC, Michel N, Haentjens J, Faivre L, Lavoute C, Nguyen K, Tregouët DA, Habib G, Charron P.

Clin Genet. 2019 Mar;95(3):356-367. doi: 10.1111/cge.13484. Epub 2018 Dec 27.

PubMed [citation]

PMID:: 30471092

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000546139.6

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

Description

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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYH6 protein function. ClinVar contains an entry for this variant (Variation ID: 228895). This missense change has been observed in individual(s) with congenital heart disease, dilated cardiomyopathy, or left ventricular noncompaction (PMID: 28991257, 30471092, 32746448). This variant is present in population databases (rs780726611, gnomAD 0.005%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1610 of the MYH6 protein (p.Arg1610Cys).

#	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: Nov 10, 2024

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