Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000148946 | SCV005077463 | likely pathogenic | Hereditary insensitivity to pain with anhidrosis | 2024-04-04 | criteria provided, single submitter | clinical testing | Variant summary: NTRK1 c.1532G>A (p.Gly511Glu) results in a non-conservative amino acid change located in the Protein kinase domain (IPR000719) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251454 control chromosomes. c.1532G>A has been reported in the literature in at-least one individual affected with features of Hereditary Insensitivity To Pain With Anhidrosis (example, Hepburn_2014 cited in Shaikh_2017). At least one publication reports experimental evidence evaluating an impact on protein function (Shaikh_2017). The most pronounced variant effect results in abolished PLC gamma signaling. The following publications have been ascertained in the context of this evaluation (PMID: 25359976, 35471943, 27676246, 30201336). ClinVar contains an entry for this variant (Variation ID: 161443). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
OMIM | RCV000148946 | SCV000195863 | pathogenic | Hereditary insensitivity to pain with anhidrosis | 2014-10-31 | no assertion criteria provided | literature only |