Submissions for variant NM_001376.5(DYNC1H1):c.13315G>A (p.Glu4439Lys) (rs142883042)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000235280	SCV000292929	uncertain significance	not provided	2017-01-24	criteria provided, single submitter	clinical testing	The E4439K variant has not been published as pathogenic, nor has it been reported as a benign polymorphism to our knowledge. It was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The E4439K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. However, in silico analysis is inconsistent in its predictions as to whether or not the E4439K variant is damaging to the protein structure/function. Additionally, other missense mutations in nearby residues have not been reported in the Human Gene Mutation Database (Stenson et al., 2014). Based on the currently available information, it is unclear whether the E4439K variant is a pathogenic variant or a rare benign variant.
Invitae	RCV001084368	SCV000651616	likely benign	Charcot-Marie-Tooth disease, axonal, type 2O	2019-12-31	criteria provided, single submitter	clinical testing