ClinVar Miner

Submissions for variant NM_021625.4(TRPV4):c.1976C>T (p.Ser659Leu) (rs779715512)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000468536 SCV000549248 uncertain significance Charcot-Marie-Tooth disease type 2C 2018-06-15 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 659 of the TRPV4 protein (p.Ser659Leu). The serine residue is weakly conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs779715512, ExAC 0.04%). This variant has not been reported in the literature in individuals with a TRPV4-related disease. ClinVar contains an entry for this variant (Variation ID: 409288). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, this variant has uncertain impact on TRPV4 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics,Fulgent Genetics RCV000765040 SCV000896237 uncertain significance Brachyrachia (short spine dysplasia); Digital arthropathy-brachydactyly, familial; Metatrophic dysplasia; Parastremmatic dwarfism; Spondylometaphyseal dysplasia, Kozlowski type; Spondyloepiphyseal dysplasia Maroteaux type; Distal spinal muscular atrophy, congenital nonprogressive; Scapuloperoneal spinal muscular atrophy; Sodium serum level quantitative trait locus 1; Charcot-Marie-Tooth disease type 2C; Avascular necrosis of femoral head, primary, 2 2018-10-31 criteria provided, single submitter clinical testing

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