Submissions for variant NM_005373.3(MPL):c.823C>A (p.Pro275Thr)

dbSNP: rs28928908

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003317037	SCV004021014	uncertain significance	not specified	2023-06-02	criteria provided, single submitter	clinical testing	Variant summary: MPL c.823C>A (p.Pro275Thr) results in a non-conservative amino acid change located in the Fibronectin type III domain (IPR003961) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251032 control chromosomes. c.823C>A has been reported in the literature in at-least one compound heterozygous individual affected with Congenital Amegakaryocytic Thrombocytopenia (example, Ballmaier_2001). To our knowledge, no variant specific experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 11133753, 24438083). No clinical diagnostic laboratories have 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	RCV004558261	SCV000035482	pathogenic	Congenital amegakaryocytic thrombocytopenia 1	2001-01-01	no assertion criteria provided	literature only
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	RCV000015224	SCV004099420	uncertain significance	Congenital amegakaryocytic thrombocytopenia	2023-10-30	no assertion criteria provided	clinical testing