ClinVar Genomic variation as it relates to human health
NM_017882.3(CLN6):c.791CCT[1] (p.Ser265del)
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_017882.3(CLN6):c.791CCT[1] (p.Ser265del)
Variation ID: 205182 Accession: VCV000205182.81
- Type and length
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Microsatellite, 3 bp
- Location
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Cytogenetic: 15q23 15: 68208280-68208282 (GRCh38) [ NCBI UCSC ] 15: 68500618-68500620 (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 Aug 7, 2015 Aug 25, 2024 Jun 3, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_017882.3:c.791CCT[1] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_060352.1:p.Ser265del inframe deletion NM_017882.3:c.794_796del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NC_000015.10:g.68208282GAG[1] NC_000015.9:g.68500620GAG[1] NG_008764.2:g.53927CCT[1] LRG_832:g.53927CCT[1] LRG_832t1:c.791CCT[1] LRG_832p1:p.Ser265del - Protein change
- S265del
- Other names
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- Canonical SPDI
- NC_000015.10:68208279:AGGAGGAG:AGGAG
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- probably has functional consequence
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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
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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
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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CLN6 | - | - |
GRCh38 GRCh37 |
764 | 780 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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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no classifications from unflagged records (1) |
no classifications from unflagged records
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Apr 11, 2024 | RCV000187114.10 | |
Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Apr 30, 2024 | RCV000195031.25 | |
Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Jun 3, 2024 | RCV000727479.36 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jan 22, 2024 | RCV000989353.16 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 10, 2021 | RCV001810435.11 |
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
(May 11, 2015)
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criteria provided, single submitter
Method: clinical testing
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Ceroid lipofuscinosis, neuronal, 6
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000247045.1
First in ClinVar: Oct 05, 2015 Last updated: Oct 05, 2015 |
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Pathogenic
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Neuronal ceroid lipofuscinosis 1
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001139644.1
First in ClinVar: Jan 13, 2020 Last updated: Jan 13, 2020 |
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Pathogenic
(Apr 13, 2021)
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criteria provided, single submitter
Method: clinical testing
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Ceroid lipofuscinosis, neuronal, 6A
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Centre for Inherited Metabolic Diseases, Karolinska University Hospital
Accession: SCV001571377.1
First in ClinVar: Apr 18, 2021 Last updated: Apr 18, 2021 |
Family history: no
Secondary finding: no
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Likely pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Ceroid lipofuscinosis, neuronal, 6A
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India
Accession: SCV001786701.1
First in ClinVar: Aug 18, 2021 Last updated: Aug 18, 2021 |
Age: 0-9 years
Sex: male
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Pathogenic
(Nov 10, 2021)
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criteria provided, single submitter
Method: clinical testing
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Ceroid lipofuscinosis, neuronal, 6A
Ceroid lipofuscinosis, neuronal, 6B (Kufs type)
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV002060242.2
First in ClinVar: Jan 15, 2022 Last updated: Nov 29, 2022 |
Comment:
NM_017882.2(CLN6):c.794_796delCCT(S265del) is an in-frame deletion variant classified as pathogenic in the context of neuronal ceroid lipofuscinosis, CLN6-related. S265del has been observed in cases with relevant … (more)
NM_017882.2(CLN6):c.794_796delCCT(S265del) is an in-frame deletion variant classified as pathogenic in the context of neuronal ceroid lipofuscinosis, CLN6-related. S265del has been observed in cases with relevant disease (PMID: 21990111, 12815591, 19135028, 29930972). Functional assessments of this variant are available in the literature (PMID: 19135028, 15265688). S265del has been observed in population frequency databases (gnomAD: AFR 0.01%). In summary, NM_017882.2(CLN6):c.794_796delCCT(S265del) is an in-frame deletion variant that has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening. (less)
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Likely pathogenic
(Nov 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002023253.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Jan 22, 2024)
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criteria provided, single submitter
Method: clinical testing
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Neuronal ceroid lipofuscinosis
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001410001.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 14, 2024 |
Comment:
This variant, c.794_796del, results in the deletion of 1 amino acid(s) of the CLN6 protein (p.Ser265del), but otherwise preserves the integrity of the reading frame. … (more)
This variant, c.794_796del, results in the deletion of 1 amino acid(s) of the CLN6 protein (p.Ser265del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs768422260, gnomAD 0.01%). This variant has been observed in individuals with neuronal ceroid lipofuscinosis type 6 (PMID: 19135028, 19520283, 30705896, 31029456). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 205182). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on CLN6 function (PMID: 15265688). For these reasons, this variant has been classified as Pathogenic. (less)
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Likely pathogenic
(Mar 25, 2024)
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criteria provided, single submitter
Method: clinical testing
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Ceroid lipofuscinosis, neuronal, 6A
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004806445.1
First in ClinVar: Apr 06, 2024 Last updated: Apr 06, 2024 |
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Pathogenic
(Apr 30, 2024)
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criteria provided, single submitter
Method: clinical testing
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Ceroid lipofuscinosis, neuronal, 6A
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV005038804.1
First in ClinVar: May 07, 2024 Last updated: May 07, 2024 |
Comment:
Detected in the homozygous state in a 6 years old living girl.
Clinical Features:
Visual loss (present) , Seizure (present) , Cerebellar ataxia (present) , Global developmental delay (present) , Cerebellar atrophy (present) , Leukoencephalopathy (present) , Developmental regression … (more)
Visual loss (present) , Seizure (present) , Cerebellar ataxia (present) , Global developmental delay (present) , Cerebellar atrophy (present) , Leukoencephalopathy (present) , Developmental regression (present) (less)
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Likely pathogenic
(Jun 03, 2024)
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criteria provided, single submitter
Method: clinical testing
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Not provided
Affected status: unknown
Allele origin:
germline
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Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001713713.2
First in ClinVar: Jun 15, 2021 Last updated: Jun 09, 2024 |
Comment:
PS4_moderate, PM4, PM3, PM2_supporting, and PP1
Number of individuals with the variant: 1
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Pathogenic
(Jun 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV002497797.16
First in ClinVar: Apr 08, 2022 Last updated: Aug 04, 2024 |
Comment:
CLN6: PP4:Strong, PM2, PM3, PM4
Number of individuals with the variant: 6
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Pathogenic
(May 27, 2022)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics Laboratory, Skane University Hospital Lund
Accession: SCV005198921.1
First in ClinVar: Aug 25, 2024 Last updated: Aug 25, 2024 |
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Uncertain significance
(Nov 18, 2014)
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Flagged submission
flagged submission
Method: clinical testing
Reason: Older claim that does not account for recent evidence
Source: ClinGen
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000240689.3
First in ClinVar: Aug 07, 2015 Last updated: Aug 07, 2015 |
Comment:
c.794_796delCCT: p.Ser265del (S265del) in exon 7 of the CLN6 gene (NM_017882.2) The normal sequence with the bases that are deleted in braces is: TCCT{CCT}TCGC. The … (more)
c.794_796delCCT: p.Ser265del (S265del) in exon 7 of the CLN6 gene (NM_017882.2) The normal sequence with the bases that are deleted in braces is: TCCT{CCT}TCGC. The c.794_796delCCT variant has been reported previously in an individual with late-infantile neuronal ceroid lipofuscinosis (Sharp et al., 2003). The c.794_796delCCT variant results in an in-frame deletion of a single Serine residue at a conserved position in the seventh transmembrane domain of the CLN6 protein (Kousi et al., 2012). However, this deletion is not expected to result in protein truncation or nonsense-mediated mRNA decay. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in PME-EPI,CHILD-EPI panel(s). (less)
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Uncertain significance
(Jun 13, 2017)
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Flagged submission
flagged submission
Method: clinical testing
Reason: Older claim that does not account for recent evidence
Source: ClinGen
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000708915.2
First in ClinVar: Oct 05, 2015 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Flagged submissions do not contribute to the aggregate classification or review status for the variant. Learn more |
Germline Functional Evidence
Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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probably has functional consequence
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Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India
Accession: SCV001786701.1
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Rapid progression of a walking disability in a 5-year-old boy with a CLN6 mutation. | Matsumoto A | Brain & development | 2019 | PMID: 31029456 |
Two cases of variant late infantile ceroid lipofuscinosis in Jordan. | Nafi O | World journal of clinical cases | 2019 | PMID: 30705896 |
The Spectrum of Movement Disorders in Childhood-Onset Lysosomal Storage Diseases. | Ebrahimi-Fakhari D | Movement disorders clinical practice | 2018 | PMID: 29930972 |
Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses. | Kousi M | Human mutation | 2012 | PMID: 21990111 |
Variant late infantile neuronal ceroid lipofuscinosis (CLN6 gene) in Saudi Arabia. | Al-Muhaizea MA | Pediatric neurology | 2009 | PMID: 19520283 |
Variant late infantile ceroid lipofuscinoses associated with novel mutations in CLN6. | Cannelli N | Biochemical and biophysical research communications | 2009 | PMID: 19135028 |
CLN6, which is associated with a lysosomal storage disease, is an endoplasmic reticulum protein. | Mole SE | Experimental cell research | 2004 | PMID: 15265688 |
Spectrum of CLN6 mutations in variant late infantile neuronal ceroid lipofuscinosis. | Sharp JD | Human mutation | 2003 | PMID: 12815591 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CLN6 | - | - | - | - |
Text-mined citations for rs768422260 ...
HelpRecord last updated Aug 25, 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.