NM_000258.3(MYL3):c.460C>T (p.Arg154Cys) AND Cardiovascular phenotype

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 31, 2024
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:: RCV000621670.4

Allele description [Variation Report for NM_000258.3(MYL3):c.460C>T (p.Arg154Cys)]

NM_000258.3(MYL3):c.460C>T (p.Arg154Cys)

Gene:

MYL3:myosin light chain 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p21.31

Genomic location:

Preferred name:

NM_000258.3(MYL3):c.460C>T (p.Arg154Cys)

HGVS:

NC_000003.12:g.46859496G>A
NG_007555.2:g.27674C>T
NM_000258.3:c.460C>TMANE SELECT
NP_000249.1:p.Arg154Cys
NP_000249.1:p.Arg154Cys
LRG_395t1:c.460C>T
LRG_395:g.27674C>T
LRG_395p1:p.Arg154Cys
NC_000003.11:g.46900986G>A
NM_000258.2:c.460C>T
c.460C>T

Protein change:

R154C

Links:

dbSNP: rs143852164

NCBI 1000 Genomes Browser:

rs143852164

Molecular consequence:

NM_000258.3:c.460C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000740255	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Jan 31, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 23283745, 27532257, 31110529, 35026164, 37431535 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000740255

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Jan 31, 2024)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

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

Multiple gene mutations, not the type of mutation, are the modifier of left ventricle hypertrophy in patients with hypertrophic cardiomyopathy.

Zou Y, Wang J, Liu X, Wang Y, Chen Y, Sun K, Gao S, Zhang C, Wang Z, Zhang Y, Feng X, Song Y, Wu Y, Zhang H, Jia L, Wang H, Wang D, Yan C, Lu M, Zhou X, Song L, Hui R.

Mol Biol Rep. 2013 Jun;40(6):3969-76. doi: 10.1007/s11033-012-2474-2. Epub 2013 Jan 3.

PubMed [citation]

PMID:: 23283745

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 (5)

Details of each submission

From Ambry Genetics, SCV000740255.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

The c.460C>T (p.R154C) alteration is located in exon 4 (coding exon 4) of the MYL3 gene. This alteration results from a C to T substitution at nucleotide position 460, causing the arginine (R) at amino acid position 154 to be replaced by a cysteine (C). Based on data from gnomAD, the T allele has an overall frequency of 0.001% (4/282804) total alleles studied. The highest observed frequency was 0.008% (2/24964) of African alleles. This variant has been reported in multiple individuals with hypertrophic cardiomyopathy (HCM) (Zou, 2013; Walsh, 2017; Bonaventura, 2019; Ware, 2022; Allouba, 2023; Ambry internal data). This amino acid position is highly conserved in available vertebrate species. This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic.

#	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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