TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8224	24895;24896;24897	chr2:178718436;178718435;178718434	chr2:179583163;179583162;179583161
N2AB	7907	23944;23945;23946	chr2:178718436;178718435;178718434	chr2:179583163;179583162;179583161
N2A	6980	21163;21164;21165	chr2:178718436;178718435;178718434	chr2:179583163;179583162;179583161
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-67
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.2079
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
K/E	rs1373569910	0.238	0.016	N	0.15	0.169	0.268211541103	gnomAD-4.0.0	1.59135E-06	None	None	None	None	N	None	0	2.28676E-05	None	0	0	None	0	0	0	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
K/A	0.4188	ambiguous	0.3319	benign	-0.295	Destabilizing	0.4	N	0.321	neutral	None	None	None	None	N
K/C	0.8061	likely_pathogenic	0.7274	pathogenic	-0.404	Destabilizing	0.992	D	0.505	neutral	None	None	None	None	N
K/D	0.4994	ambiguous	0.4325	ambiguous	0.313	Stabilizing	0.447	N	0.34	neutral	None	None	None	None	N
K/E	0.2036	likely_benign	0.1664	benign	0.364	Stabilizing	0.016	N	0.15	neutral	N	0.483918803	None	None	N
K/F	0.8089	likely_pathogenic	0.7373	pathogenic	-0.292	Destabilizing	0.972	D	0.507	neutral	None	None	None	None	N
K/G	0.4887	ambiguous	0.3825	ambiguous	-0.565	Destabilizing	0.617	D	0.427	neutral	None	None	None	None	N
K/H	0.3391	likely_benign	0.2851	benign	-0.851	Destabilizing	0.92	D	0.45	neutral	None	None	None	None	N
K/I	0.5012	ambiguous	0.4356	ambiguous	0.358	Stabilizing	0.81	D	0.524	neutral	N	0.496381206	None	None	N
K/L	0.4952	ambiguous	0.3983	ambiguous	0.358	Stabilizing	0.617	D	0.449	neutral	None	None	None	None	N
K/M	0.2752	likely_benign	0.2349	benign	0.176	Stabilizing	0.972	D	0.433	neutral	None	None	None	None	N
K/N	0.318	likely_benign	0.2716	benign	-0.038	Destabilizing	0.016	N	0.275	neutral	N	0.474125884	None	None	N
K/P	0.9055	likely_pathogenic	0.8592	pathogenic	0.17	Stabilizing	0.972	D	0.453	neutral	None	None	None	None	N
K/Q	0.1486	likely_benign	0.1276	benign	-0.168	Destabilizing	0.549	D	0.413	neutral	D	0.523938629	None	None	N
K/R	0.0972	likely_benign	0.0847	benign	-0.236	Destabilizing	0.004	N	0.215	neutral	N	0.49482923	None	None	N
K/S	0.4076	ambiguous	0.3316	benign	-0.673	Destabilizing	0.25	N	0.299	neutral	None	None	None	None	N
K/T	0.1734	likely_benign	0.151	benign	-0.442	Destabilizing	0.016	N	0.231	neutral	N	0.496984101	None	None	N
K/V	0.4904	ambiguous	0.417	ambiguous	0.17	Stabilizing	0.617	D	0.492	neutral	None	None	None	None	N
K/W	0.8224	likely_pathogenic	0.7285	pathogenic	-0.21	Destabilizing	0.992	D	0.564	neutral	None	None	None	None	N
K/Y	0.6226	likely_pathogenic	0.5355	ambiguous	0.109	Stabilizing	0.972	D	0.503	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.