NM_001365999.1(SZT2):c.5905C>T (p.Arg1969Ter) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Dec 3, 2022
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:: RCV001200332.20

Allele description [Variation Report for NM_001365999.1(SZT2):c.5905C>T (p.Arg1969Ter)]

NM_001365999.1(SZT2):c.5905C>T (p.Arg1969Ter)

Gene:

SZT2:SZT2 subunit of KICSTOR complex [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p34.2

Genomic location:

Preferred name:

NM_001365999.1(SZT2):c.5905C>T (p.Arg1969Ter)

HGVS:

NC_000001.11:g.43435200C>T
NG_029091.1:g.50316C>T
NM_001365999.1:c.5905C>TMANE SELECT
NM_015284.4:c.5734C>T
NP_001352928.1:p.Arg1969Ter
NP_056099.3:p.Arg1912Ter
NC_000001.10:g.43900871C>T
NC_000001.10:g.43900871C>T
NM_015284.3:c.5734C>T

Protein change:

R1912*

Links:

dbSNP: rs764896693

NCBI 1000 Genomes Browser:

rs764896693

Molecular consequence:

NM_001365999.1:c.5905C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_015284.4:c.5734C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001371260	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely pathogenic (Jul 1, 2020)	germline	clinical testing	Citation Link,
SCV003514989	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 3, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 23932106, 27248490, 28556953, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001371260

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Likely pathogenic
(Jul 1, 2020)

germline

clinical testing

Citation Link,

SCV003514989

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 3, 2022)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	2	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Biallelic SZT2 mutations cause infantile encephalopathy with epilepsy and dysmorphic corpus callosum.

Basel-Vanagaite L, Hershkovitz T, Heyman E, Raspall-Chaure M, Kakar N, Smirin-Yosef P, Vila-Pueyo M, Kornreich L, Thiele H, Bode H, Lagovsky I, Dahary D, Haviv A, Hubshman MW, Pasmanik-Chor M, Nürnberg P, Gothelf D, Kubisch C, Shohat M, Macaya A, Borck G.

Am J Hum Genet. 2013 Sep 5;93(3):524-9. doi: 10.1016/j.ajhg.2013.07.005. Epub 2013 Aug 8.

PubMed [citation]

PMID:: 23932106
PMCID:: PMC3769928

Early-life epileptic encephalopathy secondary to SZT2 pathogenic recessive variants.

Venkatesan C, Angle B, Millichap JJ.

Epileptic Disord. 2016 Jun 1;18(2):195-200. doi: 10.1684/epd.2016.0828.

PubMed [citation]

PMID:: 27248490

See all PubMed Citations (4)

Details of each submission

From CeGaT Center for Human Genetics Tuebingen, SCV001371260.18

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		2	not provided	not provided	not provided

From Invitae, SCV003514989.2

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 932499). This variant has not been reported in the literature in individuals affected with SZT2-related conditions. This variant is present in population databases (rs764896693, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Arg1912*) in the SZT2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SZT2 are known to be pathogenic (PMID: 23932106, 27248490, 28556953).

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

Last Updated: Apr 15, 2024

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