Submissions for variant NM_002047.4(GARS1):c.235C>T (p.Arg79Ter)

dbSNP: rs1479788149

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000579209	SCV000680884	uncertain significance	not provided	2016-09-07	criteria provided, single submitter	clinical testing	The R79X variant in the GARS gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R79X variant was not observed in approximately 5900 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret R79X as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV005091455	SCV005827653	uncertain significance	Charcot-Marie-Tooth disease type 2	2024-05-04	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg79*) in the GARS gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in GARS cause disease. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GARS-related conditions. ClinVar contains an entry for this variant (Variation ID: 488933). 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.