TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15440	46543;46544;46545	chr2:178620099;178620098;178620097	chr2:179484826;179484825;179484824
N2AB	13799	41620;41621;41622	chr2:178620099;178620098;178620097	chr2:179484826;179484825;179484824
N2A	12872	38839;38840;38841	chr2:178620099;178620098;178620097	chr2:179484826;179484825;179484824
N2B	6375	19348;19349;19350	chr2:178620099;178620098;178620097	chr2:179484826;179484825;179484824
Novex-1	6500	19723;19724;19725	chr2:178620099;178620098;178620097	chr2:179484826;179484825;179484824
Novex-2	6567	19924;19925;19926	chr2:178620099;178620098;178620097	chr2:179484826;179484825;179484824
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-106
• Domain position: 50
• Structural Position: 127
• Q(SASA): 0.5581
• 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/R	None	None	0.121	N	0.353	0.091	0.451504584351	gnomAD-4.0.0	1.60166E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.45858E-05	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	0.5357	ambiguous	0.5512	ambiguous	-0.137	Destabilizing	0.983	D	0.7	prob.neutral	None	None	None	None	N
K/C	0.8335	likely_pathogenic	0.8458	pathogenic	-0.125	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
K/D	0.7487	likely_pathogenic	0.7719	pathogenic	0.022	Stabilizing	0.998	D	0.712	prob.delet.	None	None	None	None	N
K/E	0.3143	likely_benign	0.3137	benign	0.045	Stabilizing	0.978	D	0.706	prob.neutral	N	0.448951255	None	None	N
K/F	0.8995	likely_pathogenic	0.9067	pathogenic	-0.237	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
K/G	0.6811	likely_pathogenic	0.6971	pathogenic	-0.384	Destabilizing	0.998	D	0.668	neutral	None	None	None	None	N
K/H	0.4306	ambiguous	0.4755	ambiguous	-0.776	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
K/I	0.5016	ambiguous	0.4937	ambiguous	0.447	Stabilizing	0.999	D	0.737	prob.delet.	N	0.496696274	None	None	N
K/L	0.6048	likely_pathogenic	0.6293	pathogenic	0.447	Stabilizing	0.995	D	0.668	neutral	None	None	None	None	N
K/M	0.383	ambiguous	0.372	ambiguous	0.334	Stabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
K/N	0.5338	ambiguous	0.5806	pathogenic	0.179	Stabilizing	0.997	D	0.695	prob.neutral	N	0.485199669	None	None	N
K/P	0.913	likely_pathogenic	0.9207	pathogenic	0.282	Stabilizing	0.999	D	0.71	prob.delet.	None	None	None	None	N
K/Q	0.1875	likely_benign	0.1957	benign	-0.002	Destabilizing	0.994	D	0.697	prob.neutral	N	0.481867391	None	None	N
K/R	0.098	likely_benign	0.0948	benign	-0.157	Destabilizing	0.121	N	0.353	neutral	N	0.443752706	None	None	N
K/S	0.5706	likely_pathogenic	0.5985	pathogenic	-0.336	Destabilizing	0.992	D	0.717	prob.delet.	None	None	None	None	N
K/T	0.24	likely_benign	0.2489	benign	-0.15	Destabilizing	0.997	D	0.681	prob.neutral	N	0.499471108	None	None	N
K/V	0.4702	ambiguous	0.4564	ambiguous	0.282	Stabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	N
K/W	0.874	likely_pathogenic	0.8809	pathogenic	-0.204	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
K/Y	0.7859	likely_pathogenic	0.7959	pathogenic	0.128	Stabilizing	0.999	D	0.717	prob.delet.	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.