ClinVar Miner

Submissions for variant NM_000374.5(UROD):c.424C>T (p.Arg142Ter)

gnomAD frequency: 0.00001  dbSNP: rs780227281
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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 RCV001987408 SCV002214289 pathogenic not provided 2024-10-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg142*) in the UROD gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in UROD are known to be pathogenic (PMID: 1634232, 17240319, 19233912, 19419417, 23545314). This variant is present in population databases (rs780227281, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with clinical features of porphyria cutanea tarda (PMID: 10338097). ClinVar contains an entry for this variant (Variation ID: 1436524). For these reasons, this variant has been classified as Pathogenic.
Mayo Clinic Laboratories, Mayo Clinic RCV001987408 SCV004225767 pathogenic not provided 2023-11-16 criteria provided, single submitter clinical testing PP4, PM2_moderate, PVS1
Neuberg Centre For Genomic Medicine, NCGM RCV005208173 SCV005849265 likely pathogenic Familial porphyria cutanea tarda 2023-06-22 criteria provided, single submitter clinical testing The observed stop gained c.424C>T(p.Arg142Ter) variant in UROD gene has been reported previously in compound heterozygous state in individual(s) affected with porphyria cutanea tarda (McManus et al., 1999). This variant is reported with the allele frequency of 0.0008% in the gnomAD Exomes. This variant has been reported to the ClinVar database as Pathogenic. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Loss of function variants have been previously reported to be disease causing (Gómez-Abecia et al., 2013). Computational evidence (MutationTaster - Disease causing automatic) predicts damaging effect on protein structure and function for this variant. For these reasons, this variant has been classified as Likely Pathogenic.

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