Dear All,
Recently, I find that the variant p.HGVS of ClinVar annotation may different from the HGVS Nomenclature suggestion, according to the ClinVar website description, it should follow the HGVS representations. I am not sure if my understanding of ClinVar and HGVS Nomenclature is corrected, so I post it here. I will be appreciating if anyone could help me solve my question.
Regarding the explain at HGVS website, https://varnomen.hgvs.org/recommendations/protein/variant/insertion/ If the insertion of amino acids GlnSerLys between amino acids Lys2 and Gly3 changing "Met LysGly HisGlnGlnCys" to "Met Lys <u>GlnSerLys</u> Gly HisGlnGlnCys", then the p.HGVS should be p.Lys2_Gly3insGlnSerLys
Example 1. NM_004119.2(FLT3):c.2520_2521insGGATCC (p.Asn841_Tyr842insGlySer) https://www.ncbi.nlm.nih.gov/clinvar/variation/16271/
The insertion is located between 13: 28592624-28592625 (GRCh37), if you take a look at the position in UCSC genome browser, the inserted sequence should between S840 and N841, according to the HGVS Nomenclature, this p.HGVS should be p.Ser840_Asn841insGlySer, but why the p.HGVS is p.Asn841_Tyr842insGlySer on ClinVar website?
Example 2. NM_006206.6(PDGFRA):c.1681_1682insAGAGGG (p.Val561_Ile562insGluArg) https://www.ncbi.nlm.nih.gov/clinvar/variation/13547/
The insertion sequence is between the 1st and 2nd base of Val561 (UCSC), why it should be p.Val561_Ile562insGluArg on ClinVar but not p.Arg560_Val561insGluArg ?
Best,
Lijia
I guess there is a calculation error from NCBI calculation. Your calculations are correct. @ Yu
Thank you for your comment, I guess so. I sent an email to VarNomen @ HGVS.org, they told me they think my description is correct, that of ClinVar is incorrect.