Submissions for variant NM_021625.4(TRPV4):c.1913C>T (p.Pro638Leu) (rs35058636)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000479635	SCV000565633	uncertain significance	not specified	2017-03-27	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the TRPV4 gene. The P638L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P638L variant is observed in 33/10398 (0.3%) alleles from individuals of African background, (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P638L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with TRPV4-related disorders (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae	RCV000862047	SCV001002482	likely benign	Charcot-Marie-Tooth disease axonal type 2C	2019-12-31	criteria provided, single submitter	clinical testing
Molecular Genetics Laboratory,London Health Sciences Centre	RCV001174117	SCV001337238	likely benign	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing