VCV000284580.54 - ClinVar

NM_001130987.2(DYSF):c.2668G>A (p.Glu890Lys)

Germline

Classification

criteria provided, conflicting classifications. Learn more about how ClinVar calculates review status.

Conflicting classifications of pathogenicity
Uncertain significance(8); Likely benign(1)

9 out of 10 submissions contributed to this 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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001130987.2(DYSF):c.2668G>A (p.Glu890Lys)

Variation ID: 284580 Accession: VCV000284580.54

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 2p13.2 2: 71568053 (GRCh38) [ NCBI UCSC ] 2: 71795183 (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	Dec 6, 2016	Jun 22, 2025	Jan 1, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_001130987.2:c.2668G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001124459.1:p.Glu890Lys	missense
NM_003494.4:c.2614G>A MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_003485.1:p.Glu872Lys	missense
NM_001130455.2:c.2617G>A	NP_001123927.1:p.Glu873Lys	missense
NM_001130976.2:c.2572G>A	NP_001124448.1:p.Glu858Lys	missense
NM_001130977.2:c.2572G>A	NP_001124449.1:p.Glu858Lys	missense
NM_001130978.2:c.2614G>A	NP_001124450.1:p.Glu872Lys	missense
NM_001130979.2:c.2707G>A	NP_001124451.1:p.Glu903Lys	missense
NM_001130980.2:c.2665G>A	NP_001124452.1:p.Glu889Lys	missense
NM_001130981.2:c.2665G>A	NP_001124453.1:p.Glu889Lys	missense
NM_001130982.2:c.2710G>A	NP_001124454.1:p.Glu904Lys	missense
NM_001130983.2:c.2617G>A	NP_001124455.1:p.Glu873Lys	missense
NM_001130984.2:c.2575G>A	NP_001124456.1:p.Glu859Lys	missense
NM_001130985.2:c.2668G>A	NP_001124457.1:p.Glu890Lys	missense
NM_001130986.2:c.2575G>A	NP_001124458.1:p.Glu859Lys	missense
NC_000002.12:g.71568053G>A
NC_000002.11:g.71795183G>A
NG_008694.1:g.119431G>A
LRG_845:g.119431G>A
LRG_845t1:c.2614G>A	LRG_845p1:p.Glu872Lys
LRG_845t2:c.2668G>A	LRG_845p2:p.Glu890Lys

... more HGVS ... less HGVS

Protein change

E890K, E872K, E858K, E889K, E873K, E903K, E859K, E904K

Other names

Canonical SPDI

NC_000002.12:71568052:G:A

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.

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

The Genome Aggregation Database (gnomAD), exomes 0.00007

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008

Exome Aggregation Consortium (ExAC) 0.00016

Trans-Omics for Precision Medicine (TOPMed) 0.00017

The Genome Aggregation Database (gnomAD), exomes 0.00023

The Genome Aggregation Database (gnomAD) 0.00024

The Genome Aggregation Database (gnomAD) 0.00025

Links

ClinGen: CA1706245 dbSNP: rs200049922 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.
DYSF		-	-	GRCh38 GRCh37	4241	4292

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.
Miyoshi myopathy	Uncertain significance (1)	criteria provided, single submitter	Jun 14, 2016	RCV000338669.6
Limb-girdle muscular dystrophy, recessive	Uncertain significance (1)	criteria provided, single submitter	Jun 14, 2016	RCV000393077.6
not provided	Uncertain significance (5)	criteria provided, multiple submitters, no conflicts	Dec 20, 2021	RCV000416052.39
Qualitative or quantitative defects of dysferlin	Conflicting classifications of pathogenicity (2)	criteria provided, conflicting classifications	Jan 1, 2025	RCV000531939.18
Autosomal recessive limb-girdle muscular dystrophy type 2B	Uncertain significance (1)	no assertion criteria provided	Jan 8, 2020	RCV001271795.2

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.
Uncertain significance (Jun 14, 2016) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Limb-Girdle Muscular Dystrophy, Recessive Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000431770.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016

Uncertain significance (Jun 14, 2016) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Miyoshi Muscular Dystrophy Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000431769.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016

Uncertain significance (Jan 13, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Qualitative or quantitative defects of dysferlin Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001302998.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)

Uncertain significance (May 11, 2020) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001816848.1 First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021	Comment: Identified as a single heterozygous variant in a patient with a clinical diagnosis of limb-girdle muscular dystrophy (Nallamilli et al., 2018); In silico analysis supports … (more) Identified as a single heterozygous variant in a patient with a clinical diagnosis of limb-girdle muscular dystrophy (Nallamilli et al., 2018); 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: 30564623) (less)

Uncertain significance (Dec 20, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Revvity Omics, Revvity Accession: SCV003830871.2 First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024

Uncertain significance (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005187730.1 First in ClinVar: Aug 18, 2024 Last updated: Aug 18, 2024

Likely benign (Jan 01, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Qualitative or quantitative defects of dysferlin Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000649634.10 First in ClinVar: Dec 26, 2017 Last updated: Feb 16, 2025	Publications: PubMed (1) PubMed: 28492532

Uncertain significance (Jan 22, 2016) C Contributing to aggregate classification	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000337259.5 First in ClinVar: Dec 06, 2016 Last updated: Apr 13, 2025	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DYSF Number of individuals with the variant: 4 Zygosity: Single Heterozygote Sex: mixed

Uncertain significance (Jul 01, 2016) C Contributing to aggregate classification	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: SCV000493434.38 First in ClinVar: Jan 30, 2017 Last updated: Jun 22, 2025	Number of individuals with the variant: 1

Uncertain significance (Jan 08, 2020) N Not contributing to aggregate classification	no assertion criteria provided Method: clinical testing	Limb-girdle muscular dystrophy type 2B Affected status: unknown Allele origin: germline	Natera, Inc. Accession: SCV001453235.1 First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021

Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

Comment:

Identified as a single heterozygous variant in a patient with a clinical diagnosis of limb-girdle muscular dystrophy (Nallamilli et al., 2018); 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: 30564623)

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

Title	Author	Journal	Year	Link
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DYSF	-	-	-	-

Text-mined citations for rs200049922 ...

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 Jun 22, 2025

ClinVar Genomic variation as it relates to human health

NM_001130987.2(DYSF):c.2668G>A (p.Glu890Lys)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs200049922 ...