Submissions for variant NM_032977.4(CASP10):c.1502C>T (p.Pro501Leu)

gnomAD frequency: 0.00091  dbSNP: rs148939095

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000351475	SCV000426113	likely benign	Autoimmune lymphoproliferative syndrome type 2A	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
GeneDx	RCV000481210	SCV000568682	uncertain significance	not specified	2016-06-22	criteria provided, single submitter	clinical testing	The P501L variant in the CASP10 gene has been previously reported in an individual with autoimmune lymphoproliferative syndrome who also harbored a splice site variant in the TNFRSF6 gene; this individual's healthy mother also harbored the P501L variant (Cerutti et al., 2007). In vitro studies demonstrated that this variant resulted in reduced caspase-10 activity, but did not exert a dominant negative activity on wild type protein (Cerutti et al., 2007). The P501L 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. This variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties, but occurs at a position that is not conserved. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret P501L as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000351475	SCV000644015	benign	Autoimmune lymphoproliferative syndrome type 2A	2025-01-29	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000481210	SCV002067938	benign	not specified	2021-07-06	criteria provided, single submitter	clinical testing