ClinVar Miner

Submissions for variant NM_021625.4(TRPV4):c.2584del (p.Arg862fs) (rs746597270)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000482103 SCV000572704 uncertain significance not provided 2017-01-12 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the TRPV4 gene. The c.2584delC variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.2584delC variant is observed in 5/65668 (0.001%) alleles from individuals of European background in the Exome Aggregation Consortium data set; however, it is observed in 31/8254 (0.4%) alleles, including 15 homozygous individuals in the Exome Variant Server data set (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The c.2584delC variant causes a frameshift starting with codon Arginine 862, changes this amino acid to an Alanine residue and creates a premature Stop codon at position 25 of the new reading frame, denoted p.Arg862AlafsX25. The last 10 amino acid residues are replaced by 24 aberrant residues; however, this variant is not expected to result in protein truncation or nonsense mediated decay. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000816397 SCV000956903 uncertain significance Charcot-Marie-Tooth disease axonal type 2C 2019-04-17 criteria provided, single submitter clinical testing This sequence change results in a frameshift in the TRPV4 gene (p.Arg862Alafs*25). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 10 amino acids of the TRPV4 protein and extend the protein by an additional 14 amino acids. This variant is present in population databases (rs746597270, ExAC 0.008%). This variant has not been reported in the literature in individuals with TRPV4-related disease. ClinVar contains an entry for this variant (Variation ID: 423065). 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.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000482103 SCV001148821 uncertain significance not provided 2017-01-01 criteria provided, single submitter clinical testing

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