ClinVar Miner

Submissions for variant NM_018191.4(RCBTB1):c.973C>T (p.His325Tyr)

gnomAD frequency: 0.00016  dbSNP: rs200826424
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001857843 SCV002286958 likely pathogenic not provided 2024-12-22 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 325 of the RCBTB1 protein (p.His325Tyr). This variant is present in population databases (rs200826424, gnomAD 0.2%). This missense change has been observed in individual(s) with clinical features of retinal dystrophy (PMID: 27486781). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 253018). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt RCBTB1 protein function with a negative predictive value of 80%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Center for Medical Genetics Ghent, University of Ghent RCV000239605 SCV000292419 likely pathogenic Retinitis pigmentosa no assertion criteria provided research
OMIM RCV000258084 SCV000328261 pathogenic RETINAL DYSTROPHY WITH EXTRAOCULAR ANOMALIES 2016-11-01 no assertion criteria provided literature only
PreventionGenetics, part of Exact Sciences RCV004757981 SCV005345609 likely pathogenic RCBTB1-related disorder 2024-09-19 no assertion criteria provided clinical testing The RCBTB1 c.973C>T variant is predicted to result in the amino acid substitution p.His325Tyr. This variant was reported to segregate with retinal dystrophy within a large family consistent with autosomal recessive inheritance (Coppieters et al 2016. PubMed ID: 27486781, Family F1). This variant is reported in 0.15% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. This variant is interpreted as likely pathogenic.

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