Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Centre For Genomic Medicine, |
RCV003388664 | SCV004100359 | uncertain significance | L-2-hydroxyglutaric aciduria | criteria provided, single submitter | clinical testing | The missense variant p.P441L in L2HGDH (NM_024884.3) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.P441L variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. There is a moderate physicochemical difference between proline and leucine. The p.P441L missense variant is predicted to be damaging by both SIFT and PolyPhen2. The proline residue at codon 441 of L2HGDH is conserved in all mammalian species. The nucleotide c.1322 in L2HGDH is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. |