VCV000036652.38 - ClinVar

NM_033118.4(MYLK2):c.430C>G (p.Pro144Ala)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(13)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Benign/Likely benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_033118.4(MYLK2):c.430C>G (p.Pro144Ala)

Variation ID: 36652 Accession: VCV000036652.38

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 20q11.21 20: 31820503 (GRCh38) [ NCBI UCSC ] 20: 30408306 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jun 4, 2015	Oct 20, 2024	Feb 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_033118.4:c.430C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_149109.1:p.Pro144Ala	missense
NC_000020.11:g.31820503C>G
NC_000020.10:g.30408306C>G
NG_012847.1:g.6129C>G
LRG_392:g.6129C>G
LRG_392t1:c.430C>G	LRG_392p1:p.Pro144Ala
	Q9H1R3:p.Pro144Ala

... more HGVS ... less HGVS

Protein change

P144A

Other names

p.P144A:CCT>GCT

Canonical SPDI

NC_000020.11:31820502:C:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00839 (G)

Allele frequency Help The frequency of the allele represented by this VCV record.

1000 Genomes Project 0.00839

1000 Genomes Project 30x 0.00984

The Genome Aggregation Database (gnomAD) 0.01268

Trans-Omics for Precision Medicine (TOPMed) 0.01560

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.01576

Links

ClinGen: CA138534 UniProtKB: Q9H1R3#VAR_040862 dbSNP: rs34396614 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
MYLK2		-	-	GRCh38 GRCh37	639	663

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Cardiomyopathy	Benign (2)	criteria provided, single submitter	Apr 23, 2019	RCV000030331.5
not specified	Benign (5)	criteria provided, multiple submitters, no conflicts	Mar 10, 2014	RCV000039788.10
Hypertrophic cardiomyopathy 1	Benign/Likely benign (3)	criteria provided, multiple submitters, no conflicts	Feb 1, 2024	RCV000205159.21
not provided	Benign/Likely benign (2)	criteria provided, multiple submitters, no conflicts	Feb 1, 2024	RCV003436924.11
MYLK2-related disorder	Benign (1)	no assertion criteria provided	Mar 13, 2019	RCV003964820.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Benign (Apr 04, 2012)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: not provided Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000063477.6 First in ClinVar: May 03, 2013 Last updated: Jun 04, 2015	Comment: Pro144Ala in Exon 03 of MYLK2: This variant is not expected to have clinical sig nificance because it has been identified in 2.0% (137/7018) of … (more) Pro144Ala in Exon 03 of MYLK2: This variant is not expected to have clinical sig nificance because it has been identified in 2.0% (137/7018) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs34396614). (less) Number of individuals with the variant: 55
Likely benign (May 28, 2019)	criteria provided, single submitter (Mendelics Assertion Criteria 2017) Method: clinical testing	Hypertrophic cardiomyopathy 1 Affected status: unknown Allele origin: unknown	Mendelics Accession: SCV001141228.1 First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020
Benign (Jun 24, 2013)	criteria provided, single submitter (Ng et al. (Circ Cardiovasc Genet. 2013)) Method: research	not specified Affected status: unknown Allele origin: unknown	Biesecker Lab/Clinical Genomics Section, National Institutes of Health Study: ClinSeq Accession: SCV000051575.1 First in ClinVar: Jun 04, 2015 Last updated: Jun 04, 2015 Comments (2): The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for … (more) The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for details. (less) Medical sequencing	Number of individuals with the variant: 20
Benign (Apr 23, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Cardiomyopathy Affected status: unknown Allele origin: germline	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario Accession: SCV001333471.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020
Benign (Feb 01, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Hypertrophic cardiomyopathy 1 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000261623.9 First in ClinVar: Jan 31, 2016 Last updated: Feb 20, 2024
Benign (Aug 26, 2023)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024) Method: clinical testing	Hypertrophic cardiomyopathy 1 Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV001159092.5 First in ClinVar: Feb 09, 2020 Last updated: Feb 20, 2024
Likely benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal dominant inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005208566.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Benign (Mar 10, 2014)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	not specified Affected status: yes Allele origin: germline	GeneDx Accession: SCV000170576.11 First in ClinVar: Jun 23, 2014 Last updated: Jun 04, 2015	Comment: This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more) This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
Benign (Feb 01, 2024)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV004152565.10 First in ClinVar: Nov 20, 2023 Last updated: Oct 20, 2024	Comment: MYLK2: BP4, BS1, BS2 Number of individuals with the variant: 6
Benign (Dec 09, 2013)	no assertion criteria provided Method: clinical testing	Cardiomyopathy Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000052998.2 First in ClinVar: Apr 04, 2013 Last updated: Jul 05, 2015
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, University Medical Center Utrecht Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001930483.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021
Benign (Mar 13, 2019)	no assertion criteria provided Method: clinical testing	MYLK2-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004789906.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001959027.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
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Comment:

Pro144Ala in Exon 03 of MYLK2: This variant is not expected to have clinical sig nificance because it has been identified in 2.0% (137/7018) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs34396614).

Comment:

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs34396614 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 20, 2024

ClinVar Genomic variation as it relates to human health

NM_033118.4(MYLK2):c.430C>G (p.Pro144Ala)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs34396614 ...