Submissions for variant NM_015631.6(TCTN3):c.946A>G (p.Thr316Ala)

gnomAD frequency: 0.00118  dbSNP: rs200042949

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000650532	SCV000772378	likely benign	Orofacial-digital syndrome IV; Joubert syndrome 18	2024-01-21	criteria provided, single submitter	clinical testing
GeneDx	RCV001572868	SCV001825610	uncertain significance	not provided	2021-06-01	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 26582918)
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV001572868	SCV002011626	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001572868	SCV004127153	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	TCTN3: BP4
PreventionGenetics, part of Exact Sciences	RCV003937965	SCV004751636	likely benign	TCTN3-related condition	2022-11-07	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001572868	SCV001797903	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001572868	SCV001966899	likely benign	not provided		no assertion criteria provided	clinical testing
Genetic Services Laboratory, University of Chicago	RCV003151118	SCV003840107	uncertain significance	not specified	2022-06-13	no assertion criteria provided	clinical testing	DNA sequence analysis of the TCTN3 gene demonstrated a sequence change, c.946A>G, in exon 8 that results in an amino acid change, p.Thr316Ala. This sequence change has been described in the gnomAD database with a frequency of 0.20% in the non-Finnish European subpopulation (dbSNP rs200042949). The p.Thr316Ala change affects a moderately conserved amino acid residue located in a domain of the TCTN3 protein that is known to be functional. The p.Thr316Ala substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). This sequence change does not appear to have been previously described in individuals with TCTN3-related disorders. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Thr316Ala change remains unknown at this time.