Submissions for variant NM_000355.4(TCN2):c.344del (p.Asn115fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV003400105	SCV004110310	likely pathogenic	TCN2-related disorder	2023-03-15	criteria provided, single submitter	clinical testing	The TCN2 c.344delA variant is predicted to result in a frameshift and premature protein termination (p.Asn115Thrfs*92). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Frameshift variants in TCN2 are expected to be pathogenic. This variant is interpreted as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003495335	SCV004315908	pathogenic	Transcobalamin II deficiency	2023-08-24	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with TCN2-related conditions. For these reasons, this variant has been classified as Pathogenic. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asn115Thrfs*92) in the TCN2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TCN2 are known to be pathogenic (PMID: 7980584, 20352340).