ClinVar Miner

Submissions for variant NM_021625.4(TRPV4):c.855G>T (p.Gly285=) (rs879253959)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235425 SCV000292952 uncertain significance not specified 2015-06-18 criteria provided, single submitter clinical testing The c.855 G>T variant has not been published as pathogenic, nor has it been reported as a benign polymorphism to our knowledge. The c.855 G>T variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Multiple in-silico splice prediction models predict that c.855 G>T creates a new donor site which may supplant the natural donor site and lead to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. Additionally, to our knowledge, splice variants have not been reported in the TRPV4 gene (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic or a rare benign variant.
Invitae RCV001048134 SCV001212124 uncertain significance Charcot-Marie-Tooth disease axonal type 2C 2019-12-22 criteria provided, single submitter clinical testing This sequence change affects codon 285 of the TRPV4 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the TRPV4 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TRPV4-related conditions. ClinVar contains an entry for this variant (Variation ID: 245811). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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