ClinVar Miner

Submissions for variant NM_003361.4(UMOD):c.197T>C (p.Leu66Pro)

dbSNP: rs1567311288
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine RCV002251377 SCV001434944 likely pathogenic Familial juvenile hyperuricemic nephropathy type 1 2018-10-19 criteria provided, single submitter clinical testing The c.197T>C (p.Leu66Pro) variant in the UMOD gene has been reported in one patient with familial interstitial nephropathy (Xia et al., 2015 and reviewed in 29569962). This variant is identified in a patient with clinical diagnosis of familial autosomal dominant tubulointerstitial kidney disease referred for genetic testing in our laboratory. This variant has never been reported in general population databases and is located in a region where most of the variants associated with kidney disease are reported (PMID 28781372). Multiple lines of algorithms predict deleterious effect of the p.Leu66Pro change. Therefore, this c.197T>C (p.Leu66Pro) variant in the UMOD gene is classified as likely pathogenic.
Invitae RCV000681880 SCV003461942 uncertain significance not provided 2022-02-20 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 562408). This missense change has been observed in individual(s) with hyperuricemic nephropathy (PMID: 33574344). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 66 of the UMOD protein (p.Leu66Pro).
GeneDx RCV000681880 SCV003840614 uncertain significance not provided 2023-02-16 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31068150, 29569962, 31447099, 33574344, 30586318)
3billion RCV002251377 SCV003842049 likely pathogenic Familial juvenile hyperuricemic nephropathy type 1 2023-02-23 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. The variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.64; 3Cnet: 0.86). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with UMOD related disorder (ClinVar ID: VCV000562408). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.
Gharavi Laboratory, Columbia University RCV000681880 SCV000809359 likely pathogenic not provided 2018-09-16 no assertion criteria provided research

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