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NM_000432.4(MYL2):c.64G>A (p.Glu22Lys) AND not provided

Germline classification:
Pathogenic (7 submissions)
Last evaluated:
Dec 13, 2022
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:
RCV000158914.22

Allele description

NM_000432.4(MYL2):c.64G>A (p.Glu22Lys)

Genes:
LOC114827850:VISTA enhancer hs2149 [Gene]
MYL2:myosin light chain 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q24.11
Genomic location:
Preferred name:
NM_000432.4(MYL2):c.64G>A (p.Glu22Lys)
Other names:
p.E22K:GAA>AAA
HGVS:
  • NC_000012.12:g.110919133C>T
  • NG_007554.1:g.6445G>A
  • NG_065206.1:g.281C>T
  • NM_000432.4:c.64G>AMANE SELECT
  • NP_000423.2:p.Glu22Lys
  • NP_000423.2:p.Glu22Lys
  • LRG_393t1:c.64G>A
  • LRG_393:g.6445G>A
  • LRG_393p1:p.Glu22Lys
  • NC_000012.11:g.111356937C>T
  • NM_000432.3:c.64G>A
  • P10916:p.Glu22Lys
  • p.(Glu22Lys)
Protein change:
E22K; GLU22LYS
Links:
Leiden Muscular Dystrophy (MYL2): MYL2_00003; UniProtKB: P10916#VAR_004603; OMIM: 160781.0002; dbSNP: rs104894368
NCBI 1000 Genomes Browser:
rs104894368
Molecular consequence:
  • NM_000432.4:c.64G>A - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
probably has functional consequence
Observations:
2

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000208849GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)
Pathogenic
(Apr 4, 2022)
germlineclinical testing

Citation Link,

SCV000927440Blueprint Genetics
criteria provided, single submitter

(Blueprint Genetics Variant Classification Scheme)
Pathogenic
(Oct 18, 2017)
germlineclinical testing

Citation Link,

SCV001918311Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus

See additional submitters

no assertion criteria provided
Pathogenicgermlineclinical testing

SCV001953668Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus

See additional submitters

no assertion criteria provided
Pathogenicgermlineclinical testing

SCV002501723AiLife Diagnostics, AiLife Diagnostics
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Jan 3, 2022)
germlineclinical testing

PubMed (18)
[See all records that cite these PMIDs]

SCV002585422CeGaT Center for Human Genetics Tuebingen
criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)
Pathogenic
(Sep 1, 2022)
germlineclinical testing

Citation Link,

SCV004026231Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Dec 13, 2022)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedclinical testing
not providedgermlineyes2not providednot providednot providednot providedclinical testing

Citations

PubMed

Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle.

Poetter K, Jiang H, Hassanzadeh S, Master SR, Chang A, Dalakas MC, Rayment I, Sellers JR, Fananapazir L, Epstein ND.

Nat Genet. 1996 May;13(1):63-9.

PubMed [citation]
PMID:
8673105

Hypertrophic remodelling in cardiac regulatory myosin light chain (MYL2) founder mutation carriers.

Claes GR, van Tienen FH, Lindsey P, Krapels IP, Helderman-van den Enden AT, Hoos MB, Barrois YE, Janssen JW, Paulussen AD, Sels JW, Kuijpers SH, van Tintelen JP, van den Berg MP, Heesen WF, Garcia-Pavia P, Perrot A, Christiaans I, Salemink S, Marcelis CL, Smeets HJ, Brunner HG, Volders PG, et al.

Eur Heart J. 2016 Jun 14;37(23):1815-22. doi: 10.1093/eurheartj/ehv522. Epub 2015 Oct 24.

PubMed [citation]
PMID:
26497160
See all PubMed Citations (18)

Details of each submission

From GeneDx, SCV000208849.10

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Haplotype analysis suggests this variant is a founder mutation in the Dutch population (Claes et al., 2016); Not observed at significant frequency in large population cohorts (gnomAD); Published functional studies demonstrate that E22K alters MYL2 function (Szczesna et al., 2001; Szczesna-Cordary et al., 2004; Roopnarine et al., 2003; Szczesna-Cordary et al., 2007, Farman et al., 2014; Zhang et al., 2021); 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: 14594949, 16751284, 9724616, 31513939, 17606808, 12668451, 25324513, 8673105, 12404107, 21310275, 27532257, 28166811, 28138913, 27435932, 28606303, 26497160, 28790153, 16076902, 30605904, 21896538, 10948063, 30847666, 33673806, 32665702, 32880476, 33087929, 33662488, 11102452, 33548158)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Blueprint Genetics, SCV000927440.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus, SCV001918311.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001953668.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From AiLife Diagnostics, AiLife Diagnostics, SCV002501723.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (18)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

From CeGaT Center for Human Genetics Tuebingen, SCV002585422.9

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

MYL2: PP1:Strong, PM1, PM2, PS4:Moderate

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

From Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden, SCV004026231.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

PS4, PP3, PM2_SUP, PS3

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 1, 2024