Submissions for variant NM_005373.3(MPL):c.1063A>G (p.Lys355Glu)

dbSNP: rs546510242

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000670806	SCV000795706	uncertain significance	Congenital amegakaryocytic thrombocytopenia	2017-11-13	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000867193	SCV001008391	benign	Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia	2024-01-19	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000121552	SCV002068544	uncertain significance	not specified	2020-01-14	criteria provided, single submitter	clinical testing	DNA sequence analysis of the MPL gene demonstrated a sequence change, c.1063A>G, in exon 7 that results in an amino acid change, p.Lys355Glu. This sequence change does not appear to have been previously described in patients with MPL-related disorders and has been described in the gnomAD database with a frequency of 0.42% in South Asian populations (dbSNP rs546510242). The p.Lys355Glu change affects a moderately conserved amino acid residue located in a domain of the MPL protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Lys355Glu substitution. Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Lys355Glu change remains unknown at this time.
ITMI	RCV000121552	SCV000085746	not provided	not specified	2013-09-19	no assertion provided	reference population
Birmingham Platelet Group; University of Birmingham	RCV001270539	SCV001450838	uncertain significance	Abnormal bleeding; Thrombocytopenia	2020-05-01	no assertion criteria provided	research
Natera, Inc.	RCV000670806	SCV001453982	benign	Congenital amegakaryocytic thrombocytopenia	2020-09-16	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004542901	SCV004758501	likely benign	MPL-related disorder	2022-12-09	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).