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NM_014363.6(SACS):c.6781C>A (p.Leu2261Ile)

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Interpretation:
Conflicting interpretations of pathogenicity​

Benign(3);Likely benign(2);Uncertain significance(1)

Review status:
criteria provided, conflicting interpretations
Submissions:
8 (Most recent: Sep 1, 2021)
Last evaluated:
Dec 5, 2020
Accession:
VCV000240901.10
Variation ID:
240901
Description:
single nucleotide variant
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NM_014363.6(SACS):c.6781C>A (p.Leu2261Ile)

Allele ID
241625
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
13q12.12
Genomic location
13: 23337095 (GRCh38) GRCh38 UCSC
13: 23911234 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000013.10:g.23911234G>T
NC_000013.11:g.23337095G>T
NG_012342.1:g.101608C>A
... more HGVS
Protein change
L2261I, L2114I
Other names
-
Canonical SPDI
NC_000013.11:23337094:G:T
Functional consequence
-
Global minor allele frequency (GMAF)
0.00220 (T)

Allele frequency
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00369
1000 Genomes Project 0.00220
Trans-Omics for Precision Medicine (TOPMed) 0.00326
The Genome Aggregation Database (gnomAD), exomes 0.00477
Exome Aggregation Consortium (ExAC) 0.00483
The Genome Aggregation Database (gnomAD) 0.00634
Links
ClinGen: CA6911032
dbSNP: rs146722795
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Benign/Likely benign 2 criteria provided, multiple submitters, no conflicts May 21, 2020 RCV000516875.7
Benign 1 criteria provided, single submitter Dec 5, 2020 RCV001081244.2
Conflicting interpretations of pathogenicity 5 criteria provided, conflicting interpretations Jan 13, 2018 RCV000260358.5
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
SACS - - GRCh38
GRCh37
1807 1899

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely benign
(Oct 09, 2014)
criteria provided, single submitter
Method: clinical testing
Charlevoix-Saguenay spastic ataxia
Allele origin: germline
Genome Diagnostics Laboratory, University Medical Center Utrecht
Study: VKGL Data-share Consensus
Accession: SCV000743662.1
Submitted: (Apr 17, 2018)
Evidence details
Benign
(Dec 05, 2020)
criteria provided, single submitter
Method: clinical testing
Spastic paraplegia
Allele origin: germline
Invitae
Accession: SCV000289959.6
Submitted: (Jan 07, 2021)
Evidence details
Likely benign
(May 21, 2020)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001817320.1
Submitted: (Sep 01, 2021)
Evidence details
Comment:
This variant is associated with the following publications: (PMID: 23280630, 19779133, 24457356, 28251916, 25497598)
Benign
(May 31, 2017)
criteria provided, single submitter
Method: clinical testing
Charlevoix-Saguenay spastic ataxia
Allele origin: germline
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000745005.1
Submitted: (Apr 09, 2018)
Evidence details
Benign
(Dec 26, 2018)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Athena Diagnostics Inc
Accession: SCV000614973.3
Submitted: (Sep 25, 2019)
Evidence details
Publications
PubMed (4)
Uncertain significance
(Jan 13, 2018)
criteria provided, single submitter
Method: clinical testing
Charlevoix-Saguenay spastic ataxia
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000383334.3
Submitted: (Feb 20, 2020)
Evidence details
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)
Likely benign
(Jan 04, 2020)
no assertion criteria provided
Method: clinical testing
Charlevoix-Saguenay type spastic ataxia
Allele origin: germline
Natera, Inc.
Accession: SCV001460050.1
Submitted: (Dec 28, 2020)
Evidence details
Uncertain significance
(-)
no assertion criteria provided
Method: clinical testing
Charlevoix-Saguenay spastic ataxia
Allele origin: unknown
Department of Pathology and Laboratory Medicine,Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001549049.1
Submitted: (Mar 31, 2021)
Evidence details
Comment:
The p.Leu266Ile variant was identified in the proband in trans with the SACS p.Thr458Ile variant of uncertain significance. The p.Leu2261Ile variant was previously identified in … (more)

Functional evidence

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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 this variant

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Title Author Journal Year Link
Genetic heterogeneity of motor neuropathies. Bansagi B Neurology 2017 PMID: 28251916
Exome sequencing in undiagnosed inherited and sporadic ataxias. Pyle A Brain : a journal of neurology 2015 PMID: 25497598
Abnormal retinal thickening is a common feature among patients with ARSACS-related phenotypes. Yu-Wai-Man P The British journal of ophthalmology 2014 PMID: 24457356
Design and validation of a conformation sensitive capillary electrophoresis-based mutation scanning system and automated data analysis of the more than 15 kbp-spanning coding sequence of the SACS gene. Vermeer S The Journal of molecular diagnostics : JMD 2009 PMID: 19779133

Text-mined citations for rs146722795...

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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 Sep 24, 2021