Submissions for variant NM_000518.4(HBB):c.386C>T (p.Ala129Val)

dbSNP: rs33957286

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003230367	SCV003929041	uncertain significance	not specified	2023-04-17	criteria provided, single submitter	clinical testing	Variant summary: HBB c.386C>T (p.Ala129Val) results in a non-conservative amino acid change located in the Globin domain (IPR000971) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251300 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.386C>T has been reported in the literature as Hb Sitia [beta128(H6)Ala-->Val] in a Greek female with slightly reduced red blood cell indices, mild instability of the molecule and slight modifications of the oxygen binding properties (Papassotiriou_2001). These report(s) do not provide unequivocal conclusions about association of the variant with Beta Thalassemia or Hemoglobinopathy. To our knowledge, no conclusive experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
OMIM	RCV000016850	SCV000037120	other	HEMOGLOBIN SITIA	2017-12-12	no assertion criteria provided	literature only