Submissions for variant NM_001195248.2(APTX):c.124C>T (p.Arg42Ter)

gnomAD frequency: 0.00002  dbSNP: rs201912053

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000480449	SCV000569761	likely pathogenic	not provided	2022-07-01	criteria provided, single submitter	clinical testing	Reported as a single heterozygous variant in a newborn undergoing exome sequencing through the BabySeq Project (Ceyhan-Birsoy et al., 2019); Nonsense 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: 30609409)
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000616687	SCV000731377	likely pathogenic	Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia	2017-01-03	criteria provided, single submitter	clinical testing	The p.Arg42X (NM_175073.2 c.124C>T) variant in APTX has not been reported in ind ividuals with clinical features of ataxia with oculomotor apraxia type 1. This v ariant has been identified in 3/11578 of Latino chromosomes by the Exome Aggrega tion Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs201912053). This nonsense variant leads to a premature termination codon at position 42, which is predicted to lead to a truncated or absent protein. Biallelic loss of function of the APTX gene has been associated with ataxia with oculomotor apraxia type 1. In summary, although additional studies are required to fully establish a null effect on the protein, the p.Arg42X variant in APTX is likely pathogenic for ata xia with oculomotor apraxia type 1 in an autosomal recessive manner based upon p redicted impact on protein function.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000480449	SCV001762165	pathogenic	not provided	2021-06-17	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000480449	SCV002498023	pathogenic	not provided	2024-10-01	criteria provided, single submitter	clinical testing	APTX: PVS1, PM2, PM3:Supporting
Athena Diagnostics	RCV000480449	SCV004229969	likely pathogenic	not provided	2023-09-14	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org).
Labcorp Genetics (formerly Invitae), Labcorp	RCV000480449	SCV005836784	pathogenic	not provided	2025-01-15	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg42*) in the APTX gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in APTX are known to be pathogenic (PMID: 15719174, 21465257, 23183622, 26285866). This variant is present in population databases (rs201912053, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with APTX-related conditions. ClinVar contains an entry for this variant (Variation ID: 420789). For these reasons, this variant has been classified as Pathogenic.