Submissions for variant NM_020956.2(PRX):c.*3350G>A (rs186086914)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000235591	SCV000292832	uncertain significance	not provided	2015-04-30	criteria provided, single submitter	clinical testing	The G1049S variant has not been published as pathogenic nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project; however, the 1000 Genomes Project reports G1049S was observed in 5/188 (2.7%) alleles from individuals of Colombian background, indicating it may be a rare (benign) variant in this population. This substitution occurs at a position that is not conserved, and Serine is observed at this position in other mammals. However, the G1049S 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. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic or a rare benign variant.
Invitae	RCV001088432	SCV000776144	likely benign	Charcot-Marie-Tooth disease type 4	2019-12-31	criteria provided, single submitter	clinical testing