ClinVar Miner

Submissions for variant NM_004937.3(CTNS):c.220G>A (p.Asp74Asn)

gnomAD frequency: 0.00116  dbSNP: rs139364393
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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 RCV002548331 SCV001116204 likely benign Ocular cystinosis; Juvenile nephropathic cystinosis; Inborn genetic diseases 2025-02-02 criteria provided, single submitter clinical testing
Natera, Inc. RCV001271646 SCV001452948 likely benign Cystinosis 2020-04-19 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001357584 SCV001553094 uncertain significance not provided no assertion criteria provided clinical testing The CTNS p.D74N variant was not identified in the literature but was identified in dbSNP (ID: rs139364393) and ClinVar (classified as likely benign by Invitae for Juvenile nephropathic cystinosis, Nephropathic cystinosis and Ocular cystinosis). The variant was identified in control databases in 107 of 282810 chromosomes at a frequency of 0.0003783, and was observed at the highest frequency in the African population in 87 of 24960 chromosomes (freq: 0.003486) (Genome Aggregation Database March 6, 2019, v2.1.1). The p.D74 residue is not conserved in mammals and computational analyses (MUT Assesor, PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.
PreventionGenetics, part of Exact Sciences RCV003928450 SCV004745670 likely benign CTNS-related disorder 2022-04-18 no assertion criteria provided clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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