ClinVar Miner

Submissions for variant NM_001365999.1(SZT2):c.6120_6122del (p.Val2041del) (rs746200792)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000412881 SCV000491431 likely pathogenic not provided 2016-02-15 criteria provided, single submitter clinical testing The c.5949_5951delTGT variant in the SZT2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.5949_5951delTGT variant results in an in-frame 3 base pair deletion and is predicted to cause loss of a Valine residue at position 1984 in the protein, denoted as p.Val1984del. The c.5949_5951delTGT variant was not observed at any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Thus, the c.5949_5951delTGT variant is a strong candidate for pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
CHLA Center for Personalized Medicine,Children's Hospital, Los Angeles RCV000735287 SCV000854440 likely pathogenic Cryptorchidism; Global developmental delay; Seizures; Abnormality of the anterior fontanelle; Macrocephalus; Deep plantar creases; Abnormality of the cerebral white matter; Central hypotonia criteria provided, single submitter clinical testing
Broad Institute Rare Disease Group, Broad Institute RCV001004920 SCV001164430 uncertain significance Early infantile epileptic encephalopathy 18 2018-12-03 criteria provided, single submitter research The heterozygous p.Val1984del variant was identifed by our study in the compound heterozygous state, with another VUS, in one individual with early infantile epileptic encephalopathy. This variant has been identified in 0.08865% (9/10152) of Ashkenazi Jewish chromosomes chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs756197807). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. This variant is predicted to change the protein length with the in-frame deletion of Valine (Val) at position 1984. In summary, the clinical significance of the p.Val1984del variant is uncertain. ACMG/AMP Criteria applied: PM2, PM4, PP3 (Richards 2015).
Invitae RCV000412881 SCV001393243 uncertain significance not provided 2020-02-18 criteria provided, single submitter clinical testing This variant, c.5949_5951del, results in the deletion of 1 amino acid(s) of the SZT2 protein (p.Val1984del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs746200792, ExAC 0.007%). This variant has been observed in an individual affected with early-onset epileptic encephalopathy (PMID: 30564332). ClinVar contains an entry for this variant (Variation ID: 372895). This variant has been reported to reduce mitochondrial activity and alter mitochondrial morphology in combination with a second SZT2 variant in patient fibroblasts (PMID: 30564332). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GenomeConnect, ClinGen RCV001004920 SCV001423312 not provided Early infantile epileptic encephalopathy 18 no assertion provided phenotyping only Variant interpretted as Likely pathogenic and reported on 06-02-2016 by Lab or GTR ID 506013. Variant also interpretted as Likley pathogenic and reported on 08-22-2019 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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