ClinVar Miner

Submissions for variant NM_021625.5(TRPV4):c.2012T>C (p.Leu671Pro)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002417373 SCV002720299 uncertain significance Inborn genetic diseases 2020-08-18 criteria provided, single submitter clinical testing The p.L671P variant (also known as c.2012T>C), located in coding exon 12 of the TRPV4 gene, results from a T to C substitution at nucleotide position 2012. The leucine at codon 671 is replaced by proline, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Dr. med. U. Finckh, Human Genetics, Eurofins MVZ RCV003330108 SCV003932810 likely pathogenic Neuronopathy, distal hereditary motor, autosomal dominant 8; Scapuloperoneal spinal muscular atrophy; Charcot-Marie-Tooth disease axonal type 2C 2022-03-29 criteria provided, single submitter clinical testing The variant is not present in gnomAD. Prediction tools support a damaging effect on protein function. Missense mutation is the common disease mechanism in TRPV4. The affected codon is part of the functionally important pore-forming domain of the TRPV4 ion channel (PMID: 27252279; 12715179) and is conserved in the paralogous proteins TRPV1-3. Internal data: detected in two probands with symptoms compatible with TRPV4-associated neuromuscular disease (see separate comment for details). We classify the variant as likely pathogenic. Further information however may lead to up- or downrating and therefore should be followed closely.

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