Submissions for variant NM_001355436.2(SPTB):c.6095T>C (p.Leu2032Pro)

dbSNP: rs1555366607

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Department of Hematology, 303rd Hospital of the People's Liberation Army	RCV000625738	SCV000680096	pathogenic	Hereditary spherocytosis	2018-02-03	no assertion criteria provided	clinical testing	Five genes are reported to be associated with HS, including Ankyrin (ANK1), band 3 (SLC4A1), α-spectrin (SPTA1), β-spectrin (SPTB), and protein 4.2 (EPB42). β-Spectrin, encoded by SPTB, plays an important role (He BJ 2018). A mutation in an allele of β-spectrin can lead to erythrocytosis; if both alleles are mutated, the incidence of HS increases (Perrotta S 2008). The common mutation types in SPTB often lead to defects in mRNA processing and truncated β-spectrin(Maciag M 2009). In a peripheral blood smear of the proband, spherocytosis ranged from 7% to 16%. Scores for predicting the probability of a damaging mutation using Sorting Tolerant From Intolerant (SIFT, http://sift.jcvi.org/) and Polymorphism Phenotyping v2 (PolyPhen-2, http://genetics.bwh.harvard.edu/pph2/) were high. The damaging effect of the novel SPTB mutation on the function of membrane proteins was further verified by EMA-BT and flow cytometry showed that the mean fluorescence intensity (MFI) of eosine-5-maleimide (EMA) in the erythrocytes of the patient was decreased by 47.1% (normal: <16%). In summary, the L2032P variant meets our criteria to be classified as pathogenic.