Uncertainty in exact position of a PTM on a proteoform can arise in cases where SwissProt entries have many recorded modifications and amino acid variants and fragmentation data are incomplete to assert an umambiguous level 1 proteoform. This phenomenon is exemplified by cardiac troponin C (cTnC), which was identified in its canonical form (full length, N-terminal acetylated, PFR55232) as a level 1 proteoform (Figure ). Nine additional proteoforms had sufficiently high proteoform-level Q-scores to pass FDR cutoffs due to excellent sequence coverage in regions without modifications and they were classified as level 3 proteoforms with some PTM site ambiguity (Figure ). The example of cTnC is not alone; the majority of proteoforms identified in this study are either chemically modified or bear a sequence variant, as only 33% are unmodified (Figure ). While filtering by C-score can help triage level 3 proteoforms for which PTM localization is ambiguous, the C-score does not help in cases where there is only one possible site of modification. To curate a core set of proteoforms uniquely expressed in the five individual tissue types, we implemented a conservative process to select those proteoforms with PTMs with direct fragment ion support (level 1 proteoforms 29 ). To this end, the number of matching fragment ions that bear a PTM (or amino acid variant) was counted for each proteoform spectral match (PrSM). While many mutated and modified proteoforms have supporting fragment ions (level 1), a disproportionate number of modified proteoforms were level 3 with two or fewer (Figure ). Consequently, the requirement of having >3 supporting fragment ions for modified proteoforms was added in addition to a C-Score >30. This process culled the set of 8784 unique proteoforms in Table down to 2843 level 1 tissue-specific proteoforms (Figure , Supplementary Data 1).