Submissions for variant NM_024577.3(SH3TC2):c.496G>T (p.Glu166Ter) (rs1554122847)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000521295	SCV000619629	likely pathogenic	not provided	2017-08-03	criteria provided, single submitter	clinical testing	A variant that is likely pathogenic has been identified in the SH3TC2 gene. The E166X variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The E166X nonsense variant in the SH3TC2 gene is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The E166X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Invitae	RCV000804704	SCV000944626	pathogenic	Charcot-Marie-Tooth disease type 4	2018-09-11	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu166*) in the SH3TC2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SH3TC2-related disease. ClinVar contains an entry for this variant (Variation ID: 450991). Loss-of-function variants in SH3TC2 are known to be pathogenic (PMID: 20220177, 27068304). For these reasons, this variant has been classified as Pathogenic.