Submissions for variant NM_003680.3(YARS1):c.795G>C (p.Lys265Asn) (rs141482636)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000556540	SCV000639563	uncertain significance	Charcot-Marie-Tooth disease, dominant intermediate C	2020-09-11	criteria provided, single submitter	clinical testing	This sequence change replaces lysine with asparagine at codon 265 of the YARS protein (p.Lys265Asn). The lysine residue is weakly conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is present in population databases (rs141482636, ExAC 0.01%). This variant has been reported in an individual affected with peripheral neuropathy and an unaffected control individual (PMID: 21384131). Experimental studies have shown that this missense change is non-pathogenic in a Drosophila model (PMID: 21384131). In summary, this variant is a rare missense change that is not predicted to affect protein function. It has been reported in both the population and an affected individual, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx	RCV001597164	SCV001831983	uncertain significance	not provided	2020-09-14	criteria provided, single submitter	clinical testing	Reported in an individual with Charcot-Marie-Tooth disease who also had a variant in the FIG4 gene (Leitao-Goncalves et al., 2012); Published functional studies demonstrate no damaging effect (Bervoets et al., 2019); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30643024, 31695036, 21384131, 27876679)