Submissions for variant NM_032977.4(CASP10):c.1297G>A (p.Glu433Lys)

gnomAD frequency: 0.00014  dbSNP: rs200540853

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001796776	SCV000834187	uncertain significance	Autoimmune lymphoproliferative syndrome type 2A	2024-11-25	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 433 of the CASP10 protein (p.Glu433Lys). This variant is present in population databases (rs200540853, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CASP10-related conditions. ClinVar contains an entry for this variant (Variation ID: 581392). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt CASP10 protein function with a negative predictive value of 80%. 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.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV001530166	SCV004026201	uncertain significance	not provided	2022-11-21	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001530166	SCV001744910	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001530166	SCV001970390	likely benign	not provided		no assertion criteria provided	clinical testing