NM_014363.6(SACS):c.1228_1229del (p.Leu410fs) AND Spastic paraplegia

Clinical significance:Pathogenic (Last evaluated: Apr 30, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001384946.1

Allele description [Variation Report for NM_014363.6(SACS):c.1228_1229del (p.Leu410fs)]

NM_014363.6(SACS):c.1228_1229del (p.Leu410fs)

Gene:
SACS:sacsin molecular chaperone [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
13q12.12
Genomic location:
Preferred name:
NM_014363.6(SACS):c.1228_1229del (p.Leu410fs)
HGVS:
  • NC_000013.11:g.23355384_23355385del
  • NG_012342.1:g.83319_83320del
  • NM_001278055.2:c.787_788del
  • NM_014363.6:c.1228_1229delMANE SELECT
  • NP_001264984.1:p.Leu263fs
  • NP_055178.3:p.Leu410fs
  • NC_000013.10:g.23929522_23929523del
  • NC_000013.10:g.23929523_23929524del
  • NM_014363.4:c.1228_1229delTT
Protein change:
L263fs
Links:
dbSNP: rs1057516365
NCBI 1000 Genomes Browser:
rs1057516365
Molecular consequence:
  • NM_001278055.2:c.787_788del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_014363.6:c.1228_1229del - 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
SCV001584647Invitaecriteria provided, single submitter
Pathogenic
(Apr 30, 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

Supratentorial and pontine MRI abnormalities characterize recessive spastic ataxia of Charlevoix-Saguenay. A comprehensive study of an Italian series.

Prodi E, Grisoli M, Panzeri M, Minati L, Fattori F, Erbetta A, Uziel G, D'Arrigo S, Tessa A, Ciano C, Santorelli FM, Savoiardo M, Mariotti C.

Eur J Neurol. 2013 Jan;20(1):138-46. doi: 10.1111/j.1468-1331.2012.03815.x. Epub 2012 Jul 21.

PubMed [citation]
PMID:
22816526

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, SCV001584647.1

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

Description

This sequence change creates a premature translational stop signal (p.Leu410Serfs*2) 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 SACS-related conditions (PMID: 22816526). ClinVar contains an entry for this variant (Variation ID: 370271). 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: Oct 8, 2021

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