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NM_014946.4(SPAST):c.1409A>T (p.Asp470Val) AND Hereditary spastic paraplegia 4

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 1, 2004
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000006024.4

Allele description [Variation Report for NM_014946.4(SPAST):c.1409A>T (p.Asp470Val)]

NM_014946.4(SPAST):c.1409A>T (p.Asp470Val)

Gene:
SPAST:spastin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p22.3
Genomic location:
Preferred name:
NM_014946.4(SPAST):c.1409A>T (p.Asp470Val)
HGVS:
  • NC_000002.12:g.32136964A>T
  • NG_008730.1:g.78354A>T
  • NM_001363823.2:c.1406A>T
  • NM_001363875.2:c.1310A>T
  • NM_001377959.1:c.1313A>T
  • NM_014946.4:c.1409A>TMANE SELECT
  • NM_199436.2:c.1313A>T
  • NP_001350752.1:p.Asp469Val
  • NP_001350804.1:p.Asp437Val
  • NP_001364888.1:p.Asp438Val
  • NP_055761.2:p.Asp470Val
  • NP_955468.1:p.Asp438Val
  • LRG_714:g.78354A>T
  • NC_000002.11:g.32362033A>T
  • Q9UBP0:p.Asp470Val
Protein change:
D437V; ASP470VAL
Links:
UniProtKB: Q9UBP0#VAR_027220; OMIM: 604277.0016; dbSNP: rs121908516
NCBI 1000 Genomes Browser:
rs121908516
Molecular consequence:
  • NM_001363823.2:c.1406A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001363875.2:c.1310A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377959.1:c.1313A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_014946.4:c.1409A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_199436.2:c.1313A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary spastic paraplegia 4
Synonyms:
Spastic paraplegia 4, autosomal dominant; Familial spastic paraplegia autosomal dominant 2
Identifiers:
MONDO: MONDO:0008438; MedGen: C1866855; Orphanet: 100985; OMIM: 182601

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000026206OMIM
no assertion criteria provided
Pathogenic
(Sep 1, 2004) 		germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Intragenic modifiers of hereditary spastic paraplegia due to spastin gene mutations.

Svenson IK, Kloos MT, Gaskell PC, Nance MA, Garbern JY, Hisanaga S, Pericak-Vance MA, Ashley-Koch AE, Marchuk DA.

Neurogenetics. 2004 Sep;5(3):157-64. Epub 2004 Jul 10.

PubMed [citation]
PMID:
15248095

Details of each submission

From OMIM, SCV000026206.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In 6 affected members spanning 3 generations of a family with spastic paraplegia (SPG4; 182601), Svenson et al. (2004) identified a heterozygous 1534A-T transversion in the SPAST gene, resulting in an asp470-to-val (D470V) substitution. The 3 patients with only the heterozygous D470V mutation had adult onset at ages 55, 40, and 18 years, respectively, whereas 3 patients who were compound heterozygous for the D470V mutation and the S44L (604277.0015) polymorphism had disease onset in infancy, were wheelchair-bound by age 40 years, had a stutter, and had mild to moderate cognitive deficits. Svenson et al. (2004) concluded that presence of the S44L polymorphism, in addition to the D470V mutation, modified the SPG4 phenotype in this family.

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

Last Updated: Apr 23, 2022