NM_000258.3(MYL3):c.170C>G (p.Ala57Gly) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Aug 15, 2022
Review status:: criteria provided, conflicting classifications

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:: RCV000024471.9

Allele description [Variation Report for NM_000258.3(MYL3):c.170C>G (p.Ala57Gly)]

NM_000258.3(MYL3):c.170C>G (p.Ala57Gly)

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.170C>G (p.Ala57Gly)

Other names:

p.A57G:GCC>GGC

HGVS:

NC_000003.12:g.46860813G>C
NG_007555.2:g.26357C>G
NM_000258.3:c.170C>GMANE SELECT
NP_000249.1:p.Ala57Gly
NP_000249.1:p.Ala57Gly
LRG_395t1:c.170C>G
LRG_395:g.26357C>G
LRG_395p1:p.Ala57Gly
NC_000003.11:g.46902303G>C
NM_000258.2:c.170C>G
p.(Ala57Gly)

Protein change:

A57G

Links:

Leiden Muscular Dystrophy (MYL3): MYL3_00008; dbSNP: rs139794067

NCBI 1000 Genomes Browser:

rs139794067

Molecular consequence:

NM_000258.3:c.170C>G - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

probably has functional consequence

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
SCV000045774	Leiden Muscular Dystrophy (MYL3)	no classification provided	not provided	unknown, germline	curation	PubMed (1) [See all records that cite this PMID]
SCV000208873	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Aug 15, 2022)	germline	clinical testing	Citation Link,
SCV002502800	AiLife Diagnostics, AiLife Diagnostics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 18, 2021)	germline	clinical testing	PubMed (19) [See all records that cite these PMIDs] 11174330, 20641121, 33407484, 26385864, 25856671, 23748425, 22131351, 29914921, 27153395, 27831900, 32686758, 31513939, 33726816, 33087929, 29121657, 27532257, 28518168, 31447099, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000045774

Leiden Muscular Dystrophy (MYL3)

no classification provided

not provided

unknown, germline

curation

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

SCV000208873

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Aug 15, 2022)

germline

clinical testing

Citation Link,

SCV002502800

AiLife Diagnostics, AiLife Diagnostics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Nov 18, 2021)

germline

clinical testing

PubMed (19)
[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	not provided	not provided	not provided	not provided	not provided	not provided	curation
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	not provided	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

Different expressivity of a ventricular essential myosin light chain gene Ala57Gly mutation in familial hypertrophic cardiomyopathy.

Lee W, Hwang TH, Kimura A, Park SW, Satoh M, Nishi H, Harada H, Toyama J, Park JE.

Am Heart J. 2001 Feb;141(2):184-9.

PubMed [citation]

PMID:: 11174330

Long-term outcome of 4 Korean families with hypertrophic cardiomyopathy caused by 4 different mutations.

Choi JO, Yu CW, Chun Nah J, Rang Park J, Lee BS, Jeong Choi Y, Cho BR, Lee SC, Woo Park S, Kimura A, Euy Park J.

Clin Cardiol. 2010 Jul;33(7):430-8. doi: 10.1002/clc.20795.

PubMed [citation]

PMID:: 20641121
PMCID:: PMC6653452

See all PubMed Citations (19)

Details of each submission

From Leiden Muscular Dystrophy (MYL3), SCV000045774.1

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

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

From GeneDx, SCV000208873.13

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

Description

Published functional studies are conflicting; one mouse model showed cardiac fibrosis and hypertrophy, however the same model has been previously reported to lack a hypertrophic phenotype (Kazmierczak et al., 2013; Muthu et al., 2011); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 11174330, 26443374, 27831900, 34217267, 33288880, 34293104, 34014247, 23748425, 33726816, 33087929, 33407484, 17142342, 22131351, 22957257, 21415409, 20641121, 27153395, 26385864, 25856671, 27532257, 28518168, 21885653, 29914921, 32034976, 31513939, 31447099, 32492895, 32380161, 32686758, 33803477, 28193612, 29121657, 30706179, 33935716)

#	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, SCV002502800.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (19)

#	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

Last Updated: May 7, 2024

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