Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001341407 | SCV001535279 | uncertain significance | not provided | 2020-03-31 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with LMX1B-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with arginine at codon 213 of the LMX1B protein (p.Gly213Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Neuberg Centre For Genomic Medicine, |
RCV001823198 | SCV002073285 | uncertain significance | Nail-patella syndrome | criteria provided, single submitter | clinical testing | The missense variant p.G213R in LMX1B (NM_002316.4) has been submitted to the Leiden Open Variation Database where it has been classified as Likely Pathogenic. However no clinical details or evidence for classification has been provided to allow an independent assesment. It has not been published in any individuals affected with LMX1B associated disease. The G213R variant is novel (not in any individuals) in gnomAD Exomes. The p.G213R missense variant is predicted to be damaging by both SIFT and PolyPhen2. The glycine residue at codon 213 of LMX1B is conserved in all mammalian species. The nucleotide c.637 in LMX1B is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. |