Submissions for variant NM_148960.3(CLDN19):c.535G>C (p.Gly179Arg)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Neuberg Centre For Genomic Medicine, NCGM	RCV004577254	SCV005061189	likely pathogenic	Renal hypomagnesemia 5 with ocular involvement		criteria provided, single submitter	clinical testing	The missense c.535G>C (p.Gly179Arg) variant in the CLDN19 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. A different amino acid change (p.Gly179Ser) is reported at the same position as a known pathogenic variant (Cogal et al., 2022). This variant is absent in gnomAD Exomes. The amino acid Glycine at position 179 is changed to an Arginine changing protein sequence and it might alter its composition and physico-chemical properties. Multiple lines of computational evidence (Polyphen - Damaging, SIFT - Damaging and MutationTaster - Disease causing) predict a damaging effect on protein structure and function for this variant. The amino acid change p.Gly179Arg in CLDN19 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. As different amino acid change (p.Gly179Ser) is reported at the same position as a known pathogenic variant (Cogal et al., 2022) suggesting it is an important residue, however further functional evidence required to prove pathogenicity. For these reasons, this variant has been classified as Likely Pathogenic.