Submissions for variant NM_005373.3(MPL):c.684T>A (p.Ser228Arg)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
St. Jude Molecular Pathology, St. Jude Children's Research Hospital	RCV004787084	SCV005402190	uncertain significance	Thrombocythemia 2	2023-11-28	criteria provided, single submitter	clinical testing	The MPL c.684T>A (p.Ser228Arg) missense change has a maximum subpopulation frequency of 0.012% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with MPL-associated disorders. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
PreventionGenetics, part of Exact Sciences	RCV004544015	SCV004758829	uncertain significance	MPL-related disorder	2023-11-27	no assertion criteria provided	clinical testing	The MPL c.684T>A variant is predicted to result in the amino acid substitution p.Ser228Arg. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.