Submissions for variant NM_144991.3(TSPEAR):c.1178del (p.Pro393fs)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV003037102	SCV003194827	likely pathogenic	not provided	2023-09-26	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV003037102	SCV003487207	pathogenic	not provided	2024-12-09	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Pro393Glnfs*19) in the TSPEAR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TSPEAR are known to be pathogenic (PMID: 34042254). This variant is present in population databases (rs782224965, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with TSPEAR-related conditions. ClinVar contains an entry for this variant (Variation ID: 2136295). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
CHU Sainte-Justine Research Center, University of Montreal	RCV003059996	SCV003761485	likely pathogenic	Ectodermal dysplasia 14, hair/tooth type with or without hypohidrosis	2021-04-16	criteria provided, single submitter	clinical testing