ClinVar Miner

Submissions for variant NM_005373.3(MPL):c.1664C>T (p.Thr555Ile)

gnomAD frequency: 0.00002  dbSNP: rs971458513
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001056572 SCV001221022 uncertain significance Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 555 of the MPL protein (p.Thr555Ile). The threonine residue is weakly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with MPL-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV004031784 SCV004993327 uncertain significance Inborn genetic diseases 2024-01-24 criteria provided, single submitter clinical testing The c.1664C>T (p.T555I) alteration is located in exon 12 (coding exon 12) of the MPL gene. This alteration results from a C to T substitution at nucleotide position 1664, causing the threonine (T) at amino acid position 555 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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