ClinVar Miner

Submissions for variant NM_001007792.1(NTRK1):c.1838G>A (p.Arg613Gln) (rs786205449)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001235402 SCV001408085 uncertain significance Hereditary insensitivity to pain with anhidrosis 2019-10-22 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 643 of the NTRK1 protein (p.Arg643Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in the homozygous state in an individual affected with hereditary sensory and autonomic neuropathy (PMID: 28328124). ClinVar contains an entry for this variant (Variation ID: 190988). 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: Benign; Align-GVGD: Class C3). 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. This variant disrupts the p.Arg643 amino acid residue in NTRK1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10330344, 29770739, 22653642, 11159935, 11719521). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
Developmental Genetics Unit,King Faisal Specialist Hospital & Research Centre RCV000171160 SCV000221356 likely pathogenic not provided no assertion criteria provided research

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