Submissions for variant NM_012470.4(TNPO3):c.2333A>G (p.Gln778Arg)

gnomAD frequency: 0.00001  dbSNP: rs1339666918

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002018788	SCV002264867	uncertain significance	Autosomal dominant limb-girdle muscular dystrophy type 1F	2021-05-13	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals with TNPO3-related conditions. This sequence change replaces glutamine with arginine at codon 778 of the TNPO3 protein (p.Gln778Arg). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and arginine. This variant is not present in population databases (ExAC no frequency). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Revvity Omics, Revvity	RCV002018788	SCV003827759	uncertain significance	Autosomal dominant limb-girdle muscular dystrophy type 1F	2020-03-17	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003334062	SCV004042320	uncertain significance	not provided	2023-09-01	criteria provided, single submitter	clinical testing	TNPO3: PM2:Supporting