ClinVar Miner

Submissions for variant NM_004937.3(CTNS):c.677A>G (p.Tyr226Cys)

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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 RCV003078686 SCV003475500 uncertain significance Ocular cystinosis; Juvenile nephropathic cystinosis; Inborn genetic diseases 2022-05-05 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 226 of the CTNS protein (p.Tyr226Cys). This variant is present in population databases (rs142860397, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with CTNS-related conditions. 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 expected to disrupt CTNS protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Ambry Genetics RCV003078685 SCV003722321 uncertain significance Inborn genetic diseases 2022-06-03 criteria provided, single submitter clinical testing The c.677A>G (p.Y226C) alteration is located in exon 9 (coding exon 7) of the CTNS gene. This alteration results from a A to G substitution at nucleotide position 677, causing the tyrosine (Y) at amino acid position 226 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005098861 SCV005641923 uncertain significance Ocular cystinosis; Juvenile nephropathic cystinosis; Nephropathic cystinosis 2024-03-02 criteria provided, single submitter clinical testing

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