ClinVar Miner

Submissions for variant NM_001007792.1(NTRK1):c.1976C>T (p.Pro659Leu) (rs121964868)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000013103 SCV000942069 likely pathogenic Hereditary insensitivity to pain with anhidrosis 2018-11-20 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 689 of the NTRK1 protein (p.Pro689Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with congenital insensitivity to pain with anhidrosis (PMID: 10861667). ClinVar contains an entry for this variant (Variation ID: 12310). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000013103 SCV000033350 pathogenic Hereditary insensitivity to pain with anhidrosis 2019-05-14 no assertion criteria provided literature only

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