Submissions for variant NM_003680.3(YARS1):c.260G>A (p.Trp87Ter) (rs776952611)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000520767	SCV000620224	uncertain significance	not provided	2017-08-28	criteria provided, single submitter	clinical testing	The W87X variant in the YARS 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 W87X is observed in 3/66,740 alleles (0.0045%) from individuals of non-Finnish European background in the ExAC dataset, with no homozygous control individuals reported (Lek et al., 2016). We interpret W87X as a variant of uncertain significance.
Invitae	RCV001242803	SCV001415915	uncertain significance	Charcot-Marie-Tooth disease, dominant intermediate C	2020-04-09	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Trp87*) in the YARS gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs776952611, ExAC 0.004%). This variant has not been reported in the literature in individuals with YARS-related conditions. ClinVar contains an entry for this variant (Variation ID: 451509). The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in YARS cause disease. 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.