Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000482527 | SCV000568356 | uncertain significance | not provided | 2017-03-15 | criteria provided, single submitter | clinical testing | The D707H variant in the SIM1 gene has been reported previously in the heterozygous state in multiple unrelated individuals with severe, early onset obesity, food-seeking behavior, and neurodevelopmental features, and was inherited from both obese and non-obese parents, thus demonstrating variable penetrance (Ramachandrappa et al., 2013). Although the D707H variant was also identified in controls, functional studies indicate the D707H variant results in reduced activity (Ramachandrappa et al., 2013). In addition, the D707H variant was also reported in a severely obese individual, but further details were not provided (Swarbrick et al., 2011). The D707H variant is observed in 57/66736 (0.09%) alleles from individuals of non-Finnish European background, in the ExAC dataset (Lek et al., 2016). The D707H variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret D707H as a variant of uncertain significance. |
Illumina Clinical Services Laboratory, |
RCV001158265 | SCV001319885 | uncertain significance | Obesity due to SIM1 deficiency | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Personalized Diabetes Medicine Program, |
RCV001174498 | SCV001337637 | uncertain significance | Monogenic diabetes | 2017-07-14 | criteria provided, single submitter | research | ACMG criteria: PP3 (5 predictors), BP4 (5 predictors); ClinVar with conflicting evidence (Montreal calls LB, GeneDx calls VUS); PS3 (reduced transcriptional activation PMID: 23778139)=VUS |
CHU Sainte- |
RCV000240299 | SCV000299177 | likely benign | Oromandibular-limb hypogenesis spectrum | 2016-08-12 | no assertion criteria provided | research |