ClinVar Genomic variation as it relates to human health
NM_001244008.2(KIF1A):c.920G>A (p.Arg307Gln)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001244008.2(KIF1A):c.920G>A (p.Arg307Gln)
Variation ID: 418275 Accession: VCV000418275.13
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q37.3 2: 240775889 (GRCh38) [ NCBI UCSC ] 2: 241715306 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Aug 5, 2017 Feb 28, 2024 Sep 12, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001244008.2:c.920G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001230937.1:p.Arg307Gln missense NM_001320705.2:c.920G>A NP_001307634.1:p.Arg307Gln missense NM_001330289.2:c.920G>A NP_001317218.1:p.Arg307Gln missense NM_001330290.2:c.920G>A NP_001317219.1:p.Arg307Gln missense NM_001379631.1:c.920G>A NP_001366560.1:p.Arg307Gln missense NM_001379632.1:c.920G>A NP_001366561.1:p.Arg307Gln missense NM_001379633.1:c.920G>A NP_001366562.1:p.Arg307Gln missense NM_001379634.1:c.920G>A NP_001366563.1:p.Arg307Gln missense NM_001379635.1:c.920G>A NP_001366564.1:p.Arg307Gln missense NM_001379636.1:c.920G>A NP_001366565.1:p.Arg307Gln missense NM_001379637.1:c.920G>A NP_001366566.1:p.Arg307Gln missense NM_001379638.1:c.920G>A NP_001366567.1:p.Arg307Gln missense NM_001379639.1:c.920G>A NP_001366568.1:p.Arg307Gln missense NM_001379640.1:c.920G>A NP_001366569.1:p.Arg307Gln missense NM_001379641.1:c.920G>A NP_001366570.1:p.Arg307Gln missense NM_001379642.1:c.920G>A NP_001366571.1:p.Arg307Gln missense NM_001379645.1:c.920G>A NP_001366574.1:p.Arg307Gln missense NM_001379646.1:c.920G>A NP_001366575.1:p.Arg307Gln missense NM_001379648.1:c.920G>A NP_001366577.1:p.Arg307Gln missense NM_001379649.1:c.920G>A NP_001366578.1:p.Arg307Gln missense NM_001379650.1:c.920G>A NP_001366579.1:p.Arg307Gln missense NM_001379651.1:c.920G>A NP_001366580.1:p.Arg307Gln missense NM_001379653.1:c.920G>A NP_001366582.1:p.Arg307Gln missense NM_004321.8:c.920G>A NP_004312.2:p.Arg307Gln missense NC_000002.12:g.240775889C>T NC_000002.11:g.241715306C>T NG_029724.1:g.49319G>A LRG_367:g.49319G>A LRG_367t1:c.920G>A LRG_367p1:p.Arg307Gln LRG_367t2:c.920G>A LRG_367p2:p.Arg307Gln - Protein change
- R307Q
- Other names
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- Canonical SPDI
- NC_000002.12:240775888:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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KIF1A | No evidence available | No evidence available |
GRCh38 GRCh37 |
2849 | 3052 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (1) |
criteria provided, single submitter
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Nov 12, 2021 | RCV000480291.5 | |
Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Jun 15, 2020 | RCV000496175.7 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 15, 2021 | RCV000705000.4 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 12, 2022 | RCV003419789.4 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Jan 06, 2017)
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criteria provided, single submitter
Method: clinical testing
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Mental retardation, autosomal dominant 9
Affected status: yes
Allele origin:
de novo
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Groupe Hospitalier Pitie Salpetriere, UF Genomique du Developpement, Assistance Publique Hopitaux de Paris
Accession: SCV000586758.1
First in ClinVar: Aug 05, 2017 Last updated: Aug 05, 2017 |
Comment:
neurodegenerative syndrome; Intellectual disability; hypotonia; cerebellar atrophy; optic nerve atrophy; congenital retinal dystrophy; pyramidal syndrome (Rossolimo and Babinsky signs)
Number of individuals with the variant: 1
Age: 0-9 years
Sex: female
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Likely pathogenic
(Dec 03, 2018)
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criteria provided, single submitter
Method: research
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Intellectual disability, autosomal dominant 9
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo
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Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV001164442.1
First in ClinVar: Mar 01, 2020 Last updated: Mar 01, 2020 |
Comment:
The heterozyous p.Arg307Gln variant in KIF1A was identified by our study in one individual with GLUT1 deficiency syndrome. Trio exome analysis showed this variant to … (more)
The heterozyous p.Arg307Gln variant in KIF1A was identified by our study in one individual with GLUT1 deficiency syndrome. Trio exome analysis showed this variant to be de novo. This variant was absent from large population studies and is predicted to shorten the length of the protein by three residues due to an in-frame deletion. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, although additional studies are required to fully establish its clinical significance, the p.Glu209_Pro211del variant is likely pathogenic. ACMG/AMP Criteria applied: PM2, PS2, PM4, PP3 (Richards 2015). (less)
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Likely pathogenic
(Jun 15, 2020)
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criteria provided, single submitter
Method: curation
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Intellectual disability, autosomal dominant 9
Affected status: unknown
Allele origin:
unknown
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SIB Swiss Institute of Bioinformatics
Accession: SCV001426722.1
First in ClinVar: Aug 10, 2020 Last updated: Aug 10, 2020 |
Comment:
This variant is interpreted as likely pathogenic for NESCAV syndrome, autosomal dominant. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low … (more)
This variant is interpreted as likely pathogenic for NESCAV syndrome, 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); Multiple lines of computational evidence support a deleterious effect on the gene or gene product (PP3); 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); De novo (paternity and maternity confirmed) (PS2). (less)
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Pathogenic
(Nov 12, 2021)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000565098.6
First in ClinVar: Apr 27, 2017 Last updated: Mar 04, 2023 |
Comment:
Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is … (more)
Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26354034, 27034427, 28332297, 28708303, 28970574, 32737135, 34121983, 33880452, 31785789, 31805580, 21376300, 26125038, 21820098) (less)
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Intellectual disability, autosomal dominant 9
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV004047769.1
First in ClinVar: Oct 28, 2023 Last updated: Oct 28, 2023 |
Comment:
The c.920G>A (p.Arg307Gln) missense variant in KIF1A gene has been reported in individuals affected with intellectual disability, cerebellar atrophy, spasticity and optic atrophy (Hotchkiss et … (more)
The c.920G>A (p.Arg307Gln) missense variant in KIF1A gene has been reported in individuals affected with intellectual disability, cerebellar atrophy, spasticity and optic atrophy (Hotchkiss et al., 2016; Ohba et al., 2015), and an individual with neurodevelopmental disorder (Chérot et al., 2018). The p.Arg307Gln variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. It has been submitted to ClinVar with varying interpretations: Pathogenic/Likely Pathogenic. The amino acid Arg at position 307 is changed to a Gln changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Arg307Gln in KIF1A is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic. (less)
Clinical Features:
Global developmental delay (present) , Hypotonia (present) , Visual impairment (present) , Hearing abnormality (present)
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Pathogenic
(Sep 12, 2022)
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criteria provided, single submitter
Method: clinical testing
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KIF1A-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004108521.1
First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
The KIF1A c.920G>A variant is predicted to result in the amino acid substitution p.Arg307Gln. This variant, also referred to as c.902G>A, has been documented as … (more)
The KIF1A c.920G>A variant is predicted to result in the amino acid substitution p.Arg307Gln. This variant, also referred to as c.902G>A, has been documented as de novo in multiple patients with spastic paraplegia, optic neve atrophy, brain anomalies, peripheral neuropathy, cognitive and language impairment, and motor delays (Hotchkiss et al. 2016. PubMed ID: 27034427; Patient 3 Ohba et al. 2015. PubMed ID: 26354034; Patients 8 and 9 in Nicita et al. 2020. PubMed ID: 32737135 ) and in a patient from a neurodevelopmental disorder cohort (Patient 18, Chérot et al. 2017. PubMed ID: 28708303). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant has been interpreted by multiple laboratories in ClinVar as pathogenic and likely pathogenic (https://www.ncbi.nlm.nih.gov/clinvar/variation/418275). In addition, other variants impacting the same amino acid residue (p.Arg307Gly and p.Arg307Pro) have also been reported in a patient with cerebellar ataxia (Patient 041 in Sun et al. 2019. PubMed ID: 29915382) and in twins with brain anomalies, epilepsy, and neuropathy (Patient 5A and 5B in Nemani et al. 2020. PubMed ID: 32096284). Based on this evidence, the c.920G>A (p.Arg307Gln) variant is interpreted as pathogenic. (less)
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Pathogenic
(Sep 15, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hereditary spastic paraplegia 30
Neuropathy, hereditary sensory, type 2C Intellectual disability, autosomal dominant 9
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000833977.4
First in ClinVar: Oct 10, 2018 Last updated: Feb 28, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, … (more)
For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KIF1A protein function. ClinVar contains an entry for this variant (Variation ID: 418275). This variant is also known as c.902G>A. This missense change has been observed in individual(s) with KIF1A-related conditions (PMID: 26354034, 27034427, 28708303). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with glutamine at codon 307 of the KIF1A protein (p.Arg307Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. (less)
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Germline Functional Evidence
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 germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Using medical exome sequencing to identify the causes of neurodevelopmental disorders: Experience of 2 clinical units and 216 patients. | Chérot E | Clinical genetics | 2018 | PMID: 28708303 |
Novel De Novo Mutations in KIF1A as a Cause of Hereditary Spastic Paraplegia With Progressive Central Nervous System Involvement. | Hotchkiss L | Journal of child neurology | 2016 | PMID: 27034427 |
De novo KIF1A mutations cause intellectual deficit, cerebellar atrophy, lower limb spasticity and visual disturbance. | Ohba C | Journal of human genetics | 2015 | PMID: 26354034 |
Text-mined citations for rs1064793161 ...
HelpRecord last updated Apr 06, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.