<html><head></head><body style="word-wrap: break-word; -webkit-nbsp-mode: space; -webkit-line-break: after-white-space; ">Hi,<div><br></div><div>i believe i have found an error in one of the phenotype variant annotations.</div><div><br></div><div>the variation rs6339 is listed as having the phenotype "Hereditary insensitivity to pain with anhidrosis", as sourced from the ph_omim set. However, when I have tried to identify the omim listing from which this is derived, I cannot find it.</div><div><br></div><div>In fact, I believe it might have been mis-curated to be "hereditary", when is should be congenital (or in fact, probably neither, it is just a variation with no phenotype and just a polymorphism), as summarized here:</div><div><br></div><div><a href="http://www.omim.org/entry/191315?search=rs6339&highlight=rs6339">http://www.omim.org/entry/191315?search=rs6339&highlight=rs6339</a></div><div><br></div><div><table class="entry-table" style="position: static; z-index: auto; "><tbody><tr><td class="av-name text-font"><div class=""><span class="av-number text-font"><span text=".0005 INSENSITIVITY TO PAIN, CONGENITAL, WITH ANHIDROSIS
NTRK1, GLN9TER, HIS598TYR, AND GLY607VAL [dbSNP:rs6336] [dbSNP:rs6339] [dbSNP:rs80356673]
In an Italian patient with congenital insensitivity to pain with anhidrosis (256800), Mardy et al. (1999) found homozygosity for a triple mutation in exons 1 and 15 in the NTRK1 gene, leading to 1 nonsense mutation (gln9 to ter) and 2 missense mutations (his598 to tyr; gly607 to val). Mardy et al. (1999) suggested that the gln9-to-ter mutation was the most likely cause of CIPA in this family. The missense mutations were later determined to have no effect on autophosphorylation of NTRK1 (Mardy et al., 2001), and are thus likely to be polymorphisms in this population." style="margin: -20px 0px 0px 20px; position: absolute; background: url("/static/icons/tooltip-define.gif") repeat scroll 0% 0% transparent; width: 46px; height: 26px; cursor: pointer;" id="lookup"></span>.0005</span>
<span class="av-name text-font lookup">INSENSITIVITY TO PAIN, CONGENITAL, WITH ANHIDROSIS</span>
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NTRK1, GLN9TER, HIS598TYR, AND GLY607VAL
[<a href="http://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs6336;toggle_HGVS_names=open" target="_blank">dbSNP:rs6336</a>] [<a href="http://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs6339;toggle_HGVS_names=open" target="_blank">dbSNP:rs6339</a>] [<a href="http://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs80356673;toggle_HGVS_names=open" target="_blank">dbSNP:rs80356673</a>]
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<tr><td class="av-text text-font lookup">In an Italian patient with<font class="Apple-style-span" color="#a21405"> congenital insensitivity to pain with anhidrosis</font> (<a href="http://www.omim.org/entry/256800">256800</a>), <a href="http://www.omim.org/entry/191315?search=rs6339&highlight=rs6339#reference30" class="entry-reference" title="Mardy, S., Miura, Y., Endo, F., Matsuda, I., Sztriha, L., Frossard, P., Moosa, A., Ismail, E. A. R., Macaya, A., Andria, G., Toscano, E., Gibson, W., Graham, G. E., Indo, Y. Congenital insensitivity to pain with anhidrosis: novel mutations in the TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth factor. Am. J. Hum. Genet. 64: 1570-1579, 1999. [PubMed: <a href="http://www.ncbi.nlm.nih.gov/pubmed/10330344" target="_blank" onclick="_gaq.push(['_trackEvent', 'Outbound', 'PubMed', 'ncbi.nlm.nih.gov'])">10330344</a>] [Full Text: <a href="http://linkinghub.elsevier.com/retrieve/pii/S0002-9297(07)63659-3" target="_blank" onclick="_gaq.push(['_trackEvent', 'Outbound', 'Publisher'])">Elsevier Science</a>]">Mardy et al. (1999)</a>
found homozygosity for a triple mutation in exons 1 and 15 in the NTRK1
gene, leading to 1 nonsense mutation (gln9 to ter) and 2 missense
mutations (his598 to tyr; gly607 to val). <a href="http://www.omim.org/entry/191315?search=rs6339&highlight=rs6339#reference30" class="entry-reference" title="Mardy, S., Miura, Y., Endo, F., Matsuda, I., Sztriha, L., Frossard, P., Moosa, A., Ismail, E. A. R., Macaya, A., Andria, G., Toscano, E., Gibson, W., Graham, G. E., Indo, Y. Congenital insensitivity to pain with anhidrosis: novel mutations in the TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth factor. Am. J. Hum. Genet. 64: 1570-1579, 1999. [PubMed: <a href="http://www.ncbi.nlm.nih.gov/pubmed/10330344" target="_blank" onclick="_gaq.push(['_trackEvent', 'Outbound', 'PubMed', 'ncbi.nlm.nih.gov'])">10330344</a>] [Full Text: <a href="http://linkinghub.elsevier.com/retrieve/pii/S0002-9297(07)63659-3" target="_blank" onclick="_gaq.push(['_trackEvent', 'Outbound', 'Publisher'])">Elsevier Science</a>]">Mardy et al. (1999)</a>
suggested that the gln9-to-ter mutation was the most likely cause of
CIPA in this family. <font class="Apple-style-span" color="#a21405">The missense mutations were later determined to
have no effect on autophosphorylation of NTRK1 (<a href="http://www.omim.org/entry/191315?search=rs6339&highlight=rs6339#reference29" class="entry-reference" title="Mardy, S., Miura, Y., Endo, F., Matsuda, I., Indo, Y. Congenital insensitivity to pain with anhidrosis (CIPA): effect of TRKA (NTRK1) missense mutations on autophosphorylation of the receptor tyrosine kinase for nerve growth factor. Hum. Molec. Genet. 10: 179-188, 2001. [PubMed: <a href="http://www.ncbi.nlm.nih.gov/pubmed/11159935" target="_blank" onclick="_gaq.push(['_trackEvent', 'Outbound', 'PubMed', 'ncbi.nlm.nih.gov'])">11159935</a>] [Full Text: <a href="http://hmg.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=11159935" target="_blank" onclick="_gaq.push(['_trackEvent', 'Outbound', 'Publisher'])">HighWire Press</a>]">Mardy et al., 2001</a>), and are thus likely to be polymorphisms in this population.</font></td></tr></tbody></table><div><br></div></div><div>I am unclear if you fetch this annotation from a remote source, or if your team curated this, but I think it needs to be corrected. Do I need to report this elsewhere?</div><div><br></div><div>Thanks for your time,</div><div><br></div><div>Nicole</div><div><br></div></body></html>