ClinVar Miner

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

dbSNP: rs546510242
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Total submissions: 7
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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
Invitae 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.
PreventionGenetics, part of Exact Sciences RCV004542901 SCV004758501 likely benign MPL-related disorder 2022-12-09 criteria provided, single submitter 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).
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

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