ClinVar Genomic variation as it relates to human health
NM_004937.3(CTNS):c.611ACG[1] (p.Asp205del)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_004937.3(CTNS):c.611ACG[1] (p.Asp205del)
Variation ID: 188718 Accession: VCV000188718.13
- Type and length
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Microsatellite, 3 bp
- Location
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Cytogenetic: 17p13.2 17: 3656725-3656727 (GRCh38) [ NCBI UCSC ] 17: 3560019-3560021 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Mar 29, 2015 Feb 28, 2024 Oct 16, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_004937.3:c.611ACG[1] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_004928.2:p.Asp205del inframe deletion NM_004937.3:c.614_616del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_001031681.3:c.611ACG[1] NP_001026851.2:p.Asp205del inframe deletion NM_001374492.1:c.611ACG[1] NP_001361421.1:p.Asp205del inframe deletion NM_001374493.1:c.170ACG[1] NP_001361422.1:p.Asp58del inframe deletion NM_001374494.1:c.170ACG[1] NP_001361423.1:p.Asp58del inframe deletion NM_001374495.1:c.170ACG[1] NP_001361424.1:p.Asp58del inframe deletion NM_001374496.1:c.170ACG[1] NP_001361425.1:p.Asp58del inframe deletion NC_000017.11:g.3656725ACG[1] NC_000017.10:g.3560019ACG[1] NG_012489.2:g.25258ACG[1] - Protein change
- D205del, D58del
- Other names
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- Canonical SPDI
- NC_000017.11:3656724:ACGACG:ACG
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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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 | ||
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HI score
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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. |
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CTNS | - | - |
GRCh38 GRCh37 |
501 | 904 | |
CTNS-AS1 | - | - | - | GRCh38 | - | 316 |
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. |
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Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Oct 16, 2023 | RCV000169014.11 | |
Pathogenic (2) |
criteria provided, single submitter
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Apr 25, 2022 | RCV000258027.11 | |
Pathogenic (1) |
criteria provided, single submitter
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Jun 11, 2023 | RCV002516526.9 |
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. |
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Pathogenic
(Apr 25, 2022)
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criteria provided, single submitter
Method: clinical testing
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Cystinosis
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002511700.1
First in ClinVar: May 16, 2022 Last updated: May 16, 2022 |
Comment:
Variant summary: CTNS c.614_616delACG (p.Asp205del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele … (more)
Variant summary: CTNS c.614_616delACG (p.Asp205del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein. The variant allele was found at a frequency of 1.2e-05 in 251348 control chromosomes. c.614_616delACG has been reported in the literature in individuals affected with Cystinosis in homozygous and compound heterozygous states. These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Oct 16, 2023)
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criteria provided, single submitter
Method: clinical testing
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Nephropathic cystinosis
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004212933.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Jun 11, 2023)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Ocular cystinosis Juvenile nephropathic cystinosis
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV002237871.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 28, 2024 |
Comment:
This variant is present in population databases (rs760256854, gnomAD 0.01%). This variant, c.614_616del, results in the deletion of 1 amino acid(s) of the CTNS protein … (more)
This variant is present in population databases (rs760256854, gnomAD 0.01%). This variant, c.614_616del, results in the deletion of 1 amino acid(s) of the CTNS protein (p.Asp205del), but otherwise preserves the integrity of the reading frame. This variant has been observed in individual(s) with cystinosis (PMID: 9792862, 10556299). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the CTNS protein in which other variant(s) (p.Asp205Asn) have been determined to be pathogenic (PMID: 9792862, 22528245, 28983406). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Experimental studies have shown that this variant affects CTNS function (PMID: 15128704). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 188718). (less)
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Likely pathogenic
(Mar 12, 2014)
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criteria provided, single submitter
Method: literature only
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Cystinosis
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000220155.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
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not provided
(-)
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no classification provided
Method: literature only
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Cystinosis
Affected status: yes
Allele origin:
germline
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GeneReviews
Accession: SCV000328211.2
First in ClinVar: Oct 30, 2016 Last updated: Oct 01, 2022 |
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Mutation analysis of the CTNS gene in Iranian patients with infantile nephropathic cystinosis: identification of two novel mutations. | Sadeghipour F | Human genome variation | 2017 | PMID: 28983406 |
Cystinosis. | Adam MP | - | 2017 | PMID: 20301574 |
A co-occurrence of osteogenesis imperfecta type VI and cystinosis. | Tucker T | American journal of medical genetics. Part A | 2012 | PMID: 22528245 |
Molecular pathogenesis of cystinosis: effect of CTNS mutations on the transport activity and subcellular localization of cystinosin. | Kalatzis V | Human molecular genetics | 2004 | PMID: 15128704 |
New aspects of the pathogenesis of cystinosis. | Kalatzis V | Pediatric nephrology (Berlin, Germany) | 2003 | PMID: 12644911 |
Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin. | Attard M | Human molecular genetics | 1999 | PMID: 10556299 |
CTNS mutations in an American-based population of cystinosis patients. | Shotelersuk V | American journal of human genetics | 1998 | PMID: 9792862 |
Text-mined citations for rs760256854 ...
HelpRecord last updated Apr 15, 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.