ClinVar Miner

Submissions for variant NM_152443.3(RDH12):c.709C>G (p.Leu237Val)

gnomAD frequency: 0.00001  dbSNP: rs1377743038
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001300394 SCV001489535 uncertain significance Leber congenital amaurosis 13 2024-01-31 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 237 of the RDH12 protein (p.Leu237Val). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with clinical features of RDH12-related conditions (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 989723). 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) performed at Invitae indicates that this missense variant is not expected to disrupt RDH12 protein function with a negative predictive value of 80%. This variant disrupts the p.Leu237 amino acid residue in RDH12. Other variant(s) that disrupt this residue have been observed in individuals with RDH12-related conditions (PMID: 30134391), which suggests that this may be a clinically significant amino acid residue. 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.
GeneDx RCV004774372 SCV005384554 uncertain significance not provided 2024-01-25 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc. RCV001277615 SCV001464579 uncertain significance Leber congenital amaurosis 2020-08-14 no assertion criteria provided clinical testing

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