Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Translational Genomics Group, |
RCV002279784 | SCV002567815 | likely pathogenic | Fanconi renotubular syndrome 1 | 2022-08-24 | no assertion criteria provided | clinical testing | Four heterozygous variants in GATM, p.(Pro320Ser), p.(Thr336Ala), p.(Thre336Ile) and p.(Pro341Leu), have previously been described as pathogenic for renal Fanconi syndrome with progression to kidney failure (Reichold et al JASN). All 4 variants were fully penetrant and clustered on conserved proline and threonine residues representing <5% of the protein. We identified a novel variant in GATM p.(Arg322Pro), segregating in an affected mother-daughter pair with idiopathic RFS. This variant is two amino acids downstream of a previously described pathogenic variant, p.(Pro320Ser). We perfomed molecular dynamics simulations which support pathogenicity of our novel variant through a consistent dynamic signature to pathogenic variants identified by Reichold et al. |