ClinVar Miner

Submissions for variant NM_000558.3(HBA1):c.134C>T (p.Pro45Leu)

dbSNP: rs33978134
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV002227039 SCV002506165 likely pathogenic not provided 2021-12-16 criteria provided, single submitter clinical testing The Hb Milledgeville variant (HBA1: c.134C>T; p.Pro45Leu, also known as Pro44Leu when numbered from the mature protein, rs33978134) has been found heterozygous in multiple individuals with mild erythrocytosis (see link to HbVar and references therein). This variant has been reported to have increased oxygen affinity with reduced cooperativity. This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. The proline at codon 45 is highly conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.544). Based on available information, this variant is considered to be likely pathogenic. References: Link to HbVar for Hb Milledgeville: https://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=57&.cgifields=histD
OMIM RCV000017114 SCV000037386 other HEMOGLOBIN MILLEDGEVILLE 2019-11-01 no assertion criteria provided literature only
OMIM RCV000641192 SCV000762830 pathogenic Erythrocytosis, familial, 7 1980-12-16 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.