The c.353delT pathogenic variant in the DYSF gene has been previously reported in multiple individuals with DYSF-related disorders who harbor an additional DYSF variant (Rosales et al., 2010; Walsh et al., 2011). This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The c.353delT variant causes a frameshift starting with codon Valine 118, changes this amino acid to a Alanine residue, and creates a premature stop codon at position 33 of the new reading frame, denoted p.Val118AlafsX33. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay.
ClinVar Genomic variation as it relates to human health
NM_001130987.2(DYSF):c.356del (p.Val119fs)
Germline
Classification
Help
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.
(12)
Help
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.
Pathogenic
12
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001130987.2(DYSF):c.356del (p.Val119fs)
Variation ID: 94308 Accession: VCV000094308.45
- Type and length
-
Deletion, 1 bp
- Location
-
Cytogenetic: 2p13.2 2: 71511817 (GRCh38) [ NCBI UCSC ] 2: 71738947 (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 Oct 19, 2015 Oct 20, 2024 May 7, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001130987.2:c.356del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001124459.1:p.Val119fs frameshift NM_003494.4:c.353del MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003485.1:p.Val118fs frameshift NM_003494.4:c.353delT MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_001130455.2:c.356del NP_001123927.1:p.Val119fs frameshift NM_001130976.2:c.353del NP_001124448.1:p.Val118fs frameshift NM_001130977.2:c.353del NP_001124449.1:p.Val118fs frameshift NM_001130978.2:c.353del NP_001124450.1:p.Val118fs frameshift NM_001130979.2:c.353del NP_001124451.1:p.Val118fs frameshift NM_001130980.2:c.353del NP_001124452.1:p.Val118fs frameshift NM_001130981.2:c.353del NP_001124453.1:p.Val118fs frameshift NM_001130982.2:c.356del NP_001124454.1:p.Val119fs frameshift NM_001130983.2:c.356del NP_001124455.1:p.Val119fs frameshift NM_001130984.2:c.356del NP_001124456.1:p.Val119fs frameshift NM_001130985.2:c.356del NP_001124457.1:p.Val119fs frameshift NM_001130986.2:c.356del NP_001124458.1:p.Val119fs frameshift NC_000002.12:g.71511817del NC_000002.11:g.71738947del NG_008694.1:g.63195del LRG_845:g.63195del LRG_845t1:c.353del LRG_845p1:p.Val118fs LRG_845t2:c.356del LRG_845p2:p.Val119fs - Protein change
- V119fs, V118fs
- Other names
- -
- Canonical SPDI
- NC_000002.12:71511816:T:
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe 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) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
- Links
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 | ||
|---|---|---|---|---|---|---|
| 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 |
4065 | 4114 | |
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. |
|---|---|---|---|---|
| Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Mar 15, 2017 | RCV000178878.9 | |
| Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Oct 1, 2020 | RCV000598847.32 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Mar 4, 2024 | RCV001336577.3 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Jan 25, 2024 | RCV001382515.6 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Nov 2, 2021 | RCV002498412.2 | |
| Pathogenic (1) |
criteria provided, single submitter
|
May 7, 2024 | RCV004689448.1 |
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. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Jun 11, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Limb-girdle muscular dystrophy, type 2B
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
Athena Diagnostics
Accession: SCV000255771.2
First in ClinVar: Oct 19, 2015 Last updated: Oct 19, 2015 |
|
|
|
Pathogenic
(Mar 15, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal recessive limb-girdle muscular dystrophy type 2B
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000790048.1
First in ClinVar: Oct 19, 2015 Last updated: Oct 19, 2015 |
|
|
|
Pathogenic
(Feb 05, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000709973.2
First in ClinVar: Apr 02, 2018 Last updated: Apr 02, 2018 |
Comment:
The c.353delT pathogenic variant in the DYSF gene has been previously reported in multiple individuals with DYSF-related disorders who harbor an additional DYSF variant (Rosales … (more)
The c.353delT pathogenic variant in the DYSF gene has been previously reported in multiple individuals with DYSF-related disorders who harbor an additional DYSF variant (Rosales et al., 2010; Walsh et al., 2011). This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The c.353delT variant causes a frameshift starting with codon Valine 118, changes this amino acid to a Alanine residue, and creates a premature stop codon at position 33 of the new reading frame, denoted p.Val118AlafsX33. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. (less)
|
|
|
Pathogenic
(Oct 11, 2012)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000231050.5
First in ClinVar: Jun 28, 2015 Last updated: Jul 30, 2019 |
Number of individuals with the variant: 1
Sex: mixed
|
|
|
Pathogenic
(Jan 25, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Qualitative or quantitative defects of dysferlin
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001581335.4
First in ClinVar: May 10, 2021 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Val118Alafs*33) in the DYSF gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Val118Alafs*33) in the DYSF gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DYSF are known to be pathogenic (PMID: 17698709, 20301480). This variant is present in population databases (rs398123782, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with DYSF-related conditions (PMID: 20544924, 21484829, 29382405). ClinVar contains an entry for this variant (Variation ID: 94308). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Mar 04, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Miyoshi muscular dystrophy 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV001529988.2
First in ClinVar: Mar 22, 2021 Last updated: Jun 17, 2024 |
|
|
|
Pathogenic
(Nov 02, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal recessive limb-girdle muscular dystrophy type 2B
Miyoshi muscular dystrophy 1 Distal myopathy with anterior tibial onset
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002810558.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
|
Pathogenic
(Jun 19, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002021831.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
|
|
Pathogenic
(May 07, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal recessive limb-girdle muscular dystrophy
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV005185420.1
First in ClinVar: Aug 11, 2024 Last updated: Aug 11, 2024 |
Comment:
Variant summary: DYSF c.353delT (p.Val118AlafsX33) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is … (more)
Variant summary: DYSF c.353delT (p.Val118AlafsX33) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant allele was found at a frequency of 1.3e-05 in 156358 control chromosomes. c.353delT has been reported in the literature in at-least one individual affected with Dysferlinopathies (example, Ankala_2014). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 24488599). ClinVar contains an entry for this variant (Variation ID: 94308). Based on the evidence outlined above, the variant was classified as pathogenic. (less)
|
|
|
Pathogenic
(Oct 01, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001501277.23
First in ClinVar: Mar 14, 2021 Last updated: Oct 20, 2024 |
Number of individuals with the variant: 2
|
|
|
Likely pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Autosomal recessive limb-girdle muscular dystrophy type 2B
Affected status: yes
Allele origin:
germline
|
Genomics England Pilot Project, Genomics England
Accession: SCV001760094.1
First in ClinVar: Jul 31, 2021 Last updated: Jul 31, 2021 |
|
|
|
Pathogenic
(Sep 16, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Limb-girdle muscular dystrophy type 2B
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV001457597.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
|
|
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Comment:
Comment:
This sequence change creates a premature translational stop signal (p.Val118Alafs*33) in the DYSF gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DYSF are known to be pathogenic (PMID: 17698709, 20301480). This variant is present in population databases (rs398123782, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with DYSF-related conditions (PMID: 20544924, 21484829, 29382405). ClinVar contains an entry for this variant (Variation ID: 94308). For these reasons, this variant has been classified as Pathogenic.
Comment:
Variant summary: DYSF c.353delT (p.Val118AlafsX33) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant allele was found at a frequency of 1.3e-05 in 156358 control chromosomes. c.353delT has been reported in the literature in at-least one individual affected with Dysferlinopathies (example, Ankala_2014). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 24488599). ClinVar contains an entry for this variant (Variation ID: 94308). Based on the evidence outlined above, the variant was classified as pathogenic.
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:
The c.353delT pathogenic variant in the DYSF gene has been previously reported in multiple individuals with DYSF-related disorders who harbor an additional DYSF variant (Rosales et al., 2010; Walsh et al., 2011). This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The c.353delT variant causes a frameshift starting with codon Valine 118, changes this amino acid to a Alanine residue, and creates a premature stop codon at position 33 of the new reading frame, denoted p.Val118AlafsX33. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay.
Comment:
This sequence change creates a premature translational stop signal (p.Val118Alafs*33) in the DYSF gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DYSF are known to be pathogenic (PMID: 17698709, 20301480). This variant is present in population databases (rs398123782, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with DYSF-related conditions (PMID: 20544924, 21484829, 29382405). ClinVar contains an entry for this variant (Variation ID: 94308). For these reasons, this variant has been classified as Pathogenic.
Comment:
Variant summary: DYSF c.353delT (p.Val118AlafsX33) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant allele was found at a frequency of 1.3e-05 in 156358 control chromosomes. c.353delT has been reported in the literature in at-least one individual affected with Dysferlinopathies (example, Ankala_2014). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 24488599). ClinVar contains an entry for this variant (Variation ID: 94308). Based on the evidence outlined above, the variant was classified as pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Dysferlinopathy. | Adam MP | - | 2021 | PMID: 20301480 |
| Next-Generation Sequencing to Diagnose Muscular Dystrophy, Rhabdomyolysis, and HyperCKemia. | Wu L | The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques | 2018 | PMID: 29382405 |
| The Clinical Outcome Study for dysferlinopathy: An international multicenter study. | Harris E | Neurology. Genetics | 2016 | PMID: 27602406 |
| Diagnostic overview of blood-based dysferlin protein assay for dysferlinopathies. | Ankala A | Muscle & nerve | 2014 | PMID: 24488599 |
| Progressive dysphagia in limb-girdle muscular dystrophy type 2B. | Walsh R | Muscle & nerve | 2011 | PMID: 21484829 |
| Novel diagnostic features of dysferlinopathies. | Rosales XQ | Muscle & nerve | 2010 | PMID: 20544924 |
| Phenotypic study in 40 patients with dysferlin gene mutations: high frequency of atypical phenotypes. | Nguyen K | Archives of neurology | 2007 | PMID: 17698709 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DYSF | - | - | - | - |
Text-mined citations for rs398123782 ...
HelpThese 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
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.