Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Exeter Molecular Genetics Laboratory | RCV001009621 | SCV001167185 | likely pathogenic | Slender long bone; Hyperparathyroidism; Embryonic calcium dysregulation; Metaphyseal fractures | 2018-07-20 | criteria provided, single submitter | clinical testing | The p.(Gly660Arg) variant has been reported in the gnomAD database at a low frequency (5/138,451 individuals [1/27,690]). No homozygotes were reported. (PM2_Moderate). The p.(Gly660Arg) variant was detected in trans with a pathogenic nonsense variant, p.(Arg510Ter) (PM3_Moderate). The p.Gly660 residue is conserved across 19 species (to lamprey) and has a consurf score of 9. The p.(Gly660Arg) variant is predicted by SIFT, PolyPhen and AlignGVGD to have a deleterious effect on protein function (PP3_Supporting). The TRPV6 variants were identified by a gene-agnostic inheritance based strategy. This patient presented with embryonic calcium dysregulation, with gracile long bones and ribs. Calcium homeostasis returned post-natally, indicating an embryonically active calcium channel. TRPV6 encodes a calcium channel which shows exclusive expression in the human placenta (PP4_Supporting). |