ClinVar Miner

Submissions for variant NM_001007792.1(NTRK1):c.1246C>T (p.Arg416Cys) (rs34900547)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000559015 SCV000626944 uncertain significance Hereditary insensitivity to pain with anhidrosis 2020-10-27 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 446 of the NTRK1 protein (p.Arg446Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs34900547, ExAC 0.03%). This variant has not been reported in the literature in individuals with NTRK1-related disease. ClinVar contains an entry for this variant (Variation ID: 456609). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C1). 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. 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.
Natera, Inc. RCV000559015 SCV001454777 uncertain significance Hereditary insensitivity to pain with anhidrosis 2020-09-16 no assertion criteria provided clinical testing

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