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Intellectual disability

Gene: SYT1

Green List (high evidence)

SYT1 (synaptotagmin 1)
EnsemblGeneIds (GRCh38): ENSG00000067715
EnsemblGeneIds (GRCh37): ENSG00000067715
OMIM: 185605, Gene2Phenotype
SYT1 is in 3 panels

6 reviews

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Changed Red to Green from external review comment and further publication to support gene-disease association
Created: 15 Aug 2018, 4:50 p.m.
added de novo tag
Created: 15 Aug 2018, 4:49 p.m.
Baker K et al,. (2018) PMID: 30107533 describes 11 patients with de novo heterozygous missense variaints in SYT1.
Collectively, the data confirmed that SYT1 variants are associated with a recurrent neurodevelopmental disorder, and found that each of the mutations detrimentally affect either the expression and localization, or functionality of SYT1. Variation in clinical phenotype severity, in combination with differential effects of SYT1 mutants in vitro, points toward mutation-specific mechanisms underlying neurological dysfunction. Phenotypic features of the cases include infantile hypotonia, congenital ophthalmic abnormalities, childhood-onset hyperkinetic movement disorders, motor stereotypies, and developmental delay varying in severity from moderate to profound. The functional impact was assessed by expressing rat SYT1 protein containing the equivalent human variants in wild-type mouse primary hippocampal cultures. All mutant forms of SYT1 were expressed at levels approximately equal to endogenous wild-type protein, and correctly localized to nerve terminals at rest. In summary, de novo dominant SYT1 missense mutations are associated with a recognizable neurodevelopmental syndrome, and further cases can now be diagnosed based on clinical features, electrophysiological signature and mutation characteristics. Variation in phenotype severity may reflect mutation-specific impact on the diverse physiological functions of SYT1.

Created: 15 Aug 2018, 4:43 p.m.
Comment on publications: Added publications suggested from external expert review to support upgrading of the gene to Green
Created: 15 Aug 2018, 4:35 p.m.

Zornitza Stark (Australian Genomics)

Green List (high evidence)

11 unrelated patients with a neurodevelopmental phenotype, including ID, and de novo variants in this gene just published in Brain, together with functional evidence.
Created: 14 Aug 2018, 9:28 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

  • https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awy209/5072007

Variants in this GENE are reported as part of current diagnostic practice

Caroline Wright (Sanger)

I don't know

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
INTELLECTUAL DISABILITY

Publications

Rebecca Foulger (Genomics England curator)

Red List (low evidence)

Possible DD-G2P gene for ID, and candidate ID gene in PMID:26350204. Currently insufficient evidence to include as diagnostic-grade.
Created: 31 Oct 2017, 9:24 a.m.

Publications

Lu Raymond (university of cambridge )

I don't know

Richard Scott (Genomics England Curator)

Comment on list classification: Insufficient evidence to date
Created: 8 Feb 2016, 1:21 a.m.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
Phenotypes
  • INTELLECTUAL DISABILITY
  • SYT1-associated neurodevelopmental disorder
Tags
de novo
OMIM
185605
Clinvar variants
Variants in SYT1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

15 Aug 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: syt1 has been classified as Green List (High Evidence).

15 Aug 2018, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: SYT1 were set to INTELLECTUAL DISABILITY; SYT1-associated neurodevelopmental disorder

15 Aug 2018, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: SYT1 were set to 26350204; 25705886; 30107533

12 Mar 2018, Gel status: 1

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

29 Nov 2017, Gel status: 1

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for gene SYT1 was set to ['26350204', ' 25705886']

8 Feb 2016, Gel status: 1

Gene classified by Genomics England curator

Richard Scott (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

8 Feb 2016, Gel status: 1

Gene classified by Genomics England curator

Richard Scott (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

13 Nov 2015, Gel status: 2

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 2

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

SYT1 was added to Intellectual disabilitypanel. Sources: Expert Review Amber

13 Nov 2015, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

SYT1 was created by ellenmcdonagh