ClinVar Miner

Submissions for variant NM_004153.4(ORC1):c.521C>T (p.Ala174Val)

dbSNP: rs764553903
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV003349944 SCV004061321 uncertain significance Inborn genetic diseases 2023-07-14 criteria provided, single submitter clinical testing The c.521C>T (p.A174V) alteration is located in exon 5 (coding exon 4) of the ORC1 gene. This alteration results from a C to T substitution at nucleotide position 521, causing the alanine (A) at amino acid position 174 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV003636012 SCV004562595 uncertain significance Meier-Gorlin syndrome 1 2023-09-13 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV005104089 SCV005820761 uncertain significance not provided 2024-05-23 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 174 of the ORC1 protein (p.Ala174Val). This variant is present in population databases (rs764553903, gnomAD 0.006%). 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: 2597050). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ORC1 protein function. 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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