NM_001244008.2(KIF1A):c.206C>T (p.Ser69Leu) AND Hereditary spastic paraplegia 30

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Jun 15, 2020
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001078152.5

Allele description [Variation Report for NM_001244008.2(KIF1A):c.206C>T (p.Ser69Leu)]

NM_001244008.2(KIF1A):c.206C>T (p.Ser69Leu)

Gene:

KIF1A:kinesin family member 1A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q37.3

Genomic location:

Preferred name:

NM_001244008.2(KIF1A):c.206C>T (p.Ser69Leu)

HGVS:

NC_000002.12:g.240788208G>A
NG_029724.1:g.37000C>T
NM_001244008.2:c.206C>TMANE SELECT
NM_001320705.2:c.206C>T
NM_001330289.2:c.206C>T
NM_001330290.2:c.206C>T
NM_001379631.1:c.206C>T
NM_001379632.1:c.206C>T
NM_001379633.1:c.206C>T
NM_001379634.1:c.206C>T
NM_001379635.1:c.206C>T
NM_001379636.1:c.206C>T
NM_001379637.1:c.206C>T
NM_001379638.1:c.206C>T
NM_001379639.1:c.206C>T
NM_001379640.1:c.206C>T
NM_001379641.1:c.206C>T
NM_001379642.1:c.206C>T
NM_001379645.1:c.206C>T
NM_001379646.1:c.206C>T
NM_001379648.1:c.206C>T
NM_001379649.1:c.206C>T
NM_001379650.1:c.206C>T
NM_001379651.1:c.206C>T
NM_001379653.1:c.206C>T
NM_004321.8:c.206C>T
NP_001230937.1:p.Ser69Leu
NP_001230937.1:p.Ser69Leu
NP_001307634.1:p.Ser69Leu
NP_001317218.1:p.Ser69Leu
NP_001317219.1:p.Ser69Leu
NP_001366560.1:p.Ser69Leu
NP_001366561.1:p.Ser69Leu
NP_001366562.1:p.Ser69Leu
NP_001366563.1:p.Ser69Leu
NP_001366564.1:p.Ser69Leu
NP_001366565.1:p.Ser69Leu
NP_001366566.1:p.Ser69Leu
NP_001366567.1:p.Ser69Leu
NP_001366568.1:p.Ser69Leu
NP_001366569.1:p.Ser69Leu
NP_001366570.1:p.Ser69Leu
NP_001366571.1:p.Ser69Leu
NP_001366574.1:p.Ser69Leu
NP_001366575.1:p.Ser69Leu
NP_001366577.1:p.Ser69Leu
NP_001366578.1:p.Ser69Leu
NP_001366579.1:p.Ser69Leu
NP_001366580.1:p.Ser69Leu
NP_001366582.1:p.Ser69Leu
NP_004312.2:p.Ser69Leu
NP_004312.2:p.Ser69Leu
LRG_367t1:c.206C>T
LRG_367t2:c.206C>T
LRG_367:g.37000C>T
LRG_367p1:p.Ser69Leu
LRG_367p2:p.Ser69Leu
NC_000002.11:g.241727625G>A
NM_001244008.1:c.206C>T
NM_004321.6:c.206C>T
NM_004321.7:c.206C>T
Q12756:p.Ser69Leu

Protein change:

S69L; SER69LEU

Links:

UniProtKB: Q12756#VAR_077467; OMIM: 601255.0014; dbSNP: rs786200949

NCBI 1000 Genomes Browser:

rs786200949

Molecular consequence:

NM_001244008.2:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001320705.2:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330289.2:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001330290.2:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379631.1:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379632.1:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379633.1:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379634.1:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379635.1:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379636.1:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379637.1:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379638.1:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379639.1:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379640.1:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379641.1:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379642.1:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379645.1:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379646.1:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379648.1:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379649.1:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379650.1:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379651.1:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379653.1:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004321.8:c.206C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Hereditary spastic paraplegia 30
Synonyms:: Spastic paraplegia 30, autosomal recessive; SPASTIC PARAPLEGIA 30A, AUTOSOMAL DOMINANT
Identifiers:: MONDO: MONDO:0012476; MedGen: C5235139; Orphanet: 101010; OMIM: 610357

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001244203	OMIM	no assertion criteria provided	Pathogenic (Jan 14, 2015)	germline	literature only	PubMed (4) [See all records that cite these PMIDs] 25585697, 26410750, 29159194, 31488895
SCV001426726	SIB Swiss Institute of Bioinformatics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 15, 2020)	unknown	curation	PubMed (6) [See all records that cite these PMIDs] 25585697, 26410750, 29159194, 31488895, 32096284, 25741868
SCV001451074	Paris Brain Institute, Inserm - ICM	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001244203

OMIM

no assertion criteria provided

Pathogenic
(Jan 14, 2015)

germline

literature only

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

SCV001426726

SIB Swiss Institute of Bioinformatics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jun 15, 2020)

unknown

curation

PubMed (6)
[See all records that cite these PMIDs]

SCV001451074

Paris Brain Institute, Inserm - ICM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

unknown

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	3	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	curation
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Dominant transmission of de novo KIF1A motor domain variant underlying pure spastic paraplegia.

Ylikallio E, Kim D, Isohanni P, Auranen M, Kim E, Lönnqvist T, Tyynismaa H.

Eur J Hum Genet. 2015 Oct;23(10):1427-30. doi: 10.1038/ejhg.2014.297. Epub 2015 Jan 14.

PubMed [citation]

PMID:: 25585697
PMCID:: PMC4592090

Variants in KIF1A gene in dominant and sporadic forms of hereditary spastic paraparesis.

Citterio A, Arnoldi A, Panzeri E, Merlini L, D'Angelo MG, Musumeci O, Toscano A, Bondi A, Martinuzzi A, Bresolin N, Bassi MT.

J Neurol. 2015 Dec;262(12):2684-90. doi: 10.1007/s00415-015-7899-9. Epub 2015 Sep 26.

PubMed [citation]

PMID:: 26410750

See all PubMed Citations (6)

Details of each submission

From OMIM, SCV001244203.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (4)

Description

In a father and son of Finnish descent with pure autosomal dominant spastic paraplegia-30A (SPG30A; 610357), Ylikallio et al. (2015) identified a heterozygous c.206C-T transition (c.206C-T, NM_001244008.1) in the KIF1A gene, resulting in a ser69-to-leu (S69L) substitution at a moderately conserved residue in the motor domain. The mutation, which was found by targeted next-generation sequencing and confirmed by Sanger sequencing, was demonstrated to have occurred de novo in the father. The variant was not present in the 1000 Genomes Project or Exome Variant Server databases. Functional studies of the variant and studies of patient cells were not performed.

In 4 affected members of a multigenerational Sicilian family with autosomal dominant SPG30A, Citterio et al. (2015) identified a heterozygous S69L mutation in the KIF1A gene. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the ExAC database. Functional studies of the variant and studies of patient cells were not performed.

In 3 members of a 3-generation family with SPG30A, Roda et al. (2017) identified a heterozygous S69L mutation in the KIF1A gene. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the ExAC database. Functional studies of the variant and studies of patient cells were not performed.

Pennings et al. (2020) identified a heterozygous S69L mutation in 3 members of a multigenerational family (P3) with SPG30A. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the gnomAD database. Functional studies of the variant were not performed.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From SIB Swiss Institute of Bioinformatics, SCV001426726.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (6)

Description

This variant is interpreted as likely pathogenic for spastic paraplegia 30, autosomal dominant. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); Prevalence in affected individuals statistically increased over controls (PS4 downgraded to moderate); Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PP1 moderate); Assumed de novo, but no confirmation of paternity and maternity (PM6); Missense variant in a gene that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease (PP2);

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Paris Brain Institute, Inserm - ICM, SCV001451074.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		3	not provided	not provided	not provided

Last Updated: Oct 20, 2024

ClinVar

Relating variation to medicine