Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000755558 | SCV000491044 | uncertain significance | not provided | 2017-05-11 | criteria provided, single submitter | clinical testing | The V140M variant in the LDB3 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The V140M variant was not observed in approximately 6,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The V140M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret V140M as a variant of uncertain significance. |
ARUP Laboratories, |
RCV000755558 | SCV000604096 | uncertain significance | not provided | 2017-05-26 | criteria provided, single submitter | clinical testing | The p.Val140Met variant (rs745329859) has not been reported in the medical literature nor has it been previously identified in our laboratory; however, it is listed in the ClinVar database as a variant of uncertain significance (Variation ID: 372662). It is listed in the Genome Aggregation Database (gnomAD) browser with a frequency in non-Finnish Europeans of 0.002% (identified in 2 out of 111,674 chromosomes). The valine at codon 140 is highly conserved down to Lamprey, and computational analyses suggest this variant has a significant effect on LDB3 protein structure/function (SIFT: damaging, PolyPhen2: probably damaging, and Mutation Taster: disease causing). However, based on the available information, the clinical significance of the p.Val140Met variant cannot be determined with certainty. |
Invitae | RCV001865288 | SCV002205068 | uncertain significance | Myofibrillar myopathy 4 | 2021-09-01 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 372662). This variant has not been reported in the literature in individuals affected with LDB3-related conditions. This variant is present in population databases (rs745329859, ExAC 0.001%). This sequence change replaces valine with methionine at codon 140 of the LDB3 protein (p.Val140Met). The valine residue is weakly conserved and there is a small physicochemical difference between valine and methionine. |