ClinVar Miner

Submissions for variant NM_144991.3(TSPEAR):c.38del (p.Leu13fs)

gnomAD frequency: 0.00011  dbSNP: rs778688031
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001917965 SCV002170748 pathogenic not provided 2025-01-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu13Argfs*38) 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 (rs778688031, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with clinical features of ectodermal dysplasia (PMID: 34042254; internal data). ClinVar contains an entry for this variant (Variation ID: 1399988). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences RCV003416561 SCV004117995 likely pathogenic TSPEAR-related disorder 2023-09-20 criteria provided, single submitter clinical testing The TSPEAR c.38delT variant is predicted to result in a frameshift and premature protein termination (p.Leu13Argfs*38). This variant was reported in an individual with ectodermal dysplasia and tooth agenesis along with a second nonsense variant in TSPEAR (Patient 5, Table 1, Bowles et al. 2021. PubMed ID: 34042254). This variant is reported in 0.017% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/21-46131391-CA-C). Frameshift variants in TSPEAR are expected to be pathogenic. This variant is interpreted as likely pathogenic.
GeneDx RCV001917965 SCV005079594 likely pathogenic not provided 2023-09-12 criteria provided, single submitter clinical testing Reported with a second TSPEAR variant in a patient with ectodermal dysplasia, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes, and this patient also harbored a variant in another ectodermal dysplasia gene (PMID: 34042254); 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; This variant is associated with the following publications: (PMID: 34042254)

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