TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5870	17833;17834;17835	chr2:178731057;178731056;178731055	chr2:179595784;179595783;179595782
N2AB	5553	16882;16883;16884	chr2:178731057;178731056;178731055	chr2:179595784;179595783;179595782
N2A	4626	14101;14102;14103	chr2:178731057;178731056;178731055	chr2:179595784;179595783;179595782
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-42
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.4484
• 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	None	None	0.999	N	0.569	0.444	0.455816718377	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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	0.594	likely_pathogenic	0.768	pathogenic	-0.615	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	N
K/C	0.8061	likely_pathogenic	0.9026	pathogenic	-0.722	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
K/D	0.7936	likely_pathogenic	0.9134	pathogenic	0.5	Stabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
K/E	0.3354	likely_benign	0.5723	pathogenic	0.622	Stabilizing	0.999	D	0.569	neutral	N	0.521765115	None	None	N
K/F	0.8923	likely_pathogenic	0.9492	pathogenic	-0.351	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
K/G	0.7297	likely_pathogenic	0.8629	pathogenic	-0.96	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
K/H	0.3793	ambiguous	0.496	ambiguous	-1.126	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
K/I	0.5022	ambiguous	0.6994	pathogenic	0.273	Stabilizing	1.0	D	0.756	deleterious	N	0.500446584	None	None	N
K/L	0.5657	likely_pathogenic	0.7012	pathogenic	0.273	Stabilizing	1.0	D	0.667	neutral	None	None	None	None	N
K/M	0.3614	ambiguous	0.514	ambiguous	0.031	Stabilizing	1.0	D	0.651	neutral	None	None	None	None	N
K/N	0.6372	likely_pathogenic	0.8129	pathogenic	-0.223	Destabilizing	1.0	D	0.667	neutral	N	0.517455373	None	None	N
K/P	0.961	likely_pathogenic	0.9798	pathogenic	0.006	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
K/Q	0.1771	likely_benign	0.2731	benign	-0.267	Destabilizing	1.0	D	0.645	neutral	N	0.511702837	None	None	N
K/R	0.0912	likely_benign	0.1107	benign	-0.3	Destabilizing	0.999	D	0.538	neutral	N	0.486036388	None	None	N
K/S	0.6176	likely_pathogenic	0.801	pathogenic	-1.037	Destabilizing	0.999	D	0.61	neutral	None	None	None	None	N
K/T	0.2942	likely_benign	0.4747	ambiguous	-0.698	Destabilizing	1.0	D	0.707	prob.neutral	D	0.52630693	None	None	N
K/V	0.4924	ambiguous	0.6585	pathogenic	0.006	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
K/W	0.8498	likely_pathogenic	0.9137	pathogenic	-0.167	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
K/Y	0.7573	likely_pathogenic	0.8583	pathogenic	0.133	Stabilizing	1.0	D	0.703	prob.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.