Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV001152783 | SCV001314015 | 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. |
Prevention |
RCV004738169 | SCV005363469 | uncertain significance | SIM1-related disorder | 2024-06-13 | no assertion criteria provided | clinical testing | The SIM1 c.2108G>A variant is predicted to result in the amino acid substitution p.Arg703Gln. This variant was reported in a single individual with severe early-onset obesity. The p.Arg703Gln substitution was reported to have no effect on SIM1 transactivation in a reporter gene assay, though the authors note the physiological relevance of the transactivation assay is unknown (Ramachandrappa et al 2013. PubMed ID: 23778139, Supplementary Table 1). This variant is reported in 0.0040% of alleles in individuals of European (Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |