Submissions for variant NM_005068.3(SIM1):c.226G>A (p.Val76Ile)

gnomAD frequency: 0.00001  dbSNP: rs756912317

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001152894	SCV001314133	uncertain significance	Obesity due to SIM1 deficiency	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
PreventionGenetics, part of Exact Sciences	RCV004738171	SCV005364522	uncertain significance	SIM1-related disorder	2023-12-18	no assertion criteria provided	clinical testing	The SIM1 c.226G>A variant is predicted to result in the amino acid substitution p.Val76Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00089% of alleles in individuals of European (Non-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.