ClinVar Miner

Submissions for variant NM_001007792.1(NTRK1):c.1696C>T (p.Arg566Ter) (rs763758904)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000760429 SCV000890312 pathogenic not provided 2018-06-06 criteria provided, single submitter clinical testing The R596X variant in the NTRK1 gene has been reported previously in association with CIPA (Miura et al., 2000). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R596X variant is not observed in large population cohorts (Lek et al., 2016). We interpret R596X as a pathogenic variant.
Invitae RCV001222355 SCV001394452 pathogenic Hereditary insensitivity to pain with anhidrosis 2020-03-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg596*) in the NTRK1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs763758904, ExAC 0.007%). This variant has been observed in combination with another NTRK1 variant in individuals affected with congenital insensitivity to pain with anhidrosis (PMID: 27265460, 29770739, 28981924). This variant is also known as c.1804C>T p.Arg602* in the literature. ClinVar contains an entry for this variant (Variation ID: 620139). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Loss-of-function variants in NTRK1 are known to be pathogenic (PMID: 10982191). For these reasons, this variant has been classified as Pathogenic.
Inherited Neuropathy Consortium RCV000789608 SCV000928971 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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