ClinVar Miner

Submissions for variant NM_004153.4(ORC1):c.608C>T (p.Thr203Ile)

gnomAD frequency: 0.00005  dbSNP: rs202095223
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000500202 SCV000596173 uncertain significance not specified 2015-10-29 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000660447 SCV000782540 uncertain significance Meier-Gorlin syndrome 1 2016-11-30 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000660447 SCV001252850 uncertain significance Meier-Gorlin syndrome 1 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.
Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital RCV000660447 SCV001984291 uncertain significance Meier-Gorlin syndrome 1 2020-03-25 criteria provided, single submitter clinical testing
Invitae RCV001857137 SCV002185117 uncertain significance not provided 2022-07-09 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 203 of the ORC1 protein (p.Thr203Ile). This variant is present in population databases (rs202095223, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ORC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 436115). 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 tolerated. 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.

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