NM_014363.6(SACS):c.1769_1770del (p.Val590fs) AND Spastic paraplegia

Clinical significance:Pathogenic (Last evaluated: Sep 15, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001389169.1

Allele description [Variation Report for NM_014363.6(SACS):c.1769_1770del (p.Val590fs)]

NM_014363.6(SACS):c.1769_1770del (p.Val590fs)

Gene:
SACS:sacsin molecular chaperone [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
13q12.12
Genomic location:
Preferred name:
NM_014363.6(SACS):c.1769_1770del (p.Val590fs)
HGVS:
  • NC_000013.11:g.23354842CA[1]
  • NG_012342.1:g.83858TG[1]
  • NM_001278055.2:c.1328_1329del
  • NM_014363.6:c.1769_1770delMANE SELECT
  • NP_001264984.1:p.Val443fs
  • NP_055178.3:p.Val590fs
  • NC_000013.10:g.23928981CA[1]
  • NC_000013.10:g.23928981_23928982del
Protein change:
V443fs
Links:
Molecular consequence:
  • NM_001278055.2:c.1328_1329del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_014363.6:c.1769_1770del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Spastic paraplegia
Synonyms:
Spastic paraplegia, lower limb
Identifiers:
MedGen: C0037772; Human Phenotype Ontology: HP:0001258

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001590436Invitaecriteria provided, single submitter
Pathogenic
(Sep 15, 2020)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

New practical definitions for the diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay.

Pilliod J, Moutton S, Lavie J, Maurat E, Hubert C, Bellance N, Anheim M, Forlani S, Mochel F, N'Guyen K, Thauvin-Robinet C, Verny C, Milea D, Lesca G, Koenig M, Rodriguez D, Houcinat N, Van-Gils J, Durand CM, Guichet A, Barth M, Bonneau D, et al.

Ann Neurol. 2015 Dec;78(6):871-86. doi: 10.1002/ana.24509. Epub 2015 Nov 14.

PubMed [citation]
PMID:
26288984

ARSACS in the Dutch population: a frequent cause of early-onset cerebellar ataxia.

Vermeer S, Meijer RP, Pijl BJ, Timmermans J, Cruysberg JR, Bos MM, Schelhaas HJ, van de Warrenburg BP, Knoers NV, Scheffer H, Kremer B.

Neurogenetics. 2008 Jul;9(3):207-14. doi: 10.1007/s10048-008-0131-7. Epub 2008 May 9. Erratum in: Neurogenetics. 2009 Feb;10(1):87.

PubMed [citation]
PMID:
18465152
PMCID:
PMC2441586
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001590436.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Val590Alafs*55) in the SACS gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with spastic ataxia of Charlevoix–Saguenay (ARSACS) (PMID: 26288984). Loss-of-function variants in SACS are known to be pathogenic (PMID: 18465152, 20876471). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 14, 2021

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