ClinVar Miner

Submissions for variant NM_004239.4(TRIP11):c.4726C>T (p.Arg1576Cys)

gnomAD frequency: 0.00002  dbSNP: rs763206653
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001233425 SCV001406018 uncertain significance Achondrogenesis, type IA 2019-11-14 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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with TRIP11-related conditions. This variant is present in population databases (rs763206653, ExAC 0.01%). This sequence change replaces arginine with cysteine at codon 1576 of the TRIP11 protein (p.Arg1576Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine.
Neuberg Centre For Genomic Medicine, NCGM RCV003448379 SCV004176648 uncertain significance Odontochondrodysplasia 1 2023-02-14 criteria provided, single submitter clinical testing The missense c.4726C>T(p.Arg1576Cys) variant in TRIP11 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant is reported with an allele frequency of 0.0004% in the gnomAD exomes database and is novel (not in any individuals) in 1000 Genomes database. This variant has been reported to the ClinVar database as Uncertain significance. The amino acid change p.Arg1576Cys in TRIP11 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Arg at position 1576 is changed to a Cys changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Variant of Uncertain Significance (VUS).
Ambry Genetics RCV004033202 SCV004971607 uncertain significance Inborn genetic diseases 2023-11-22 criteria provided, single submitter clinical testing The c.4726C>T (p.R1576C) alteration is located in exon 13 (coding exon 13) of the TRIP11 gene. This alteration results from a C to T substitution at nucleotide position 4726, causing the arginine (R) at amino acid position 1576 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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