ClinVar Miner

Submissions for variant NM_001033855.3(DCLRE1C):c.1333C>T (p.Arg445Cys)

gnomAD frequency: 0.00002  dbSNP: rs774273800
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000174696 SCV000226049 uncertain significance not provided 2018-01-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002516641 SCV003458825 uncertain significance Severe combined immunodeficiency due to DCLRE1C deficiency 2022-03-12 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 445 of the DCLRE1C protein (p.Arg445Cys). This variant is present in population databases (rs774273800, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with DCLRE1C-related conditions. ClinVar contains an entry for this variant (Variation ID: 194346). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Neuberg Centre For Genomic Medicine, NCGM RCV004720244 SCV005329507 uncertain significance Histiocytic medullary reticulosis 2023-05-20 criteria provided, single submitter clinical testing The observed missense variant c.1333C>T (p.Arg445Cys) in the DCLRE1C gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with the allele frequency 0.002% in the gnomAD Exomes. This variant has been reported to the ClinVar database as Uncertain significance. However no details are availble for independent assessment. The amino acid Arginine at position 445 is changed to a Cysteine changing protein sequence and it might alter its composition and physico-chemical properties. Computational evidence (Polyphen - Possibly Damaging) predict a damaging effect on protein structure and function for this variant. The residue is conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.

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