TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9054	27385;27386;27387	chr2:178712865;178712864;178712863	chr2:179577592;179577591;179577590
N2AB	8737	26434;26435;26436	chr2:178712865;178712864;178712863	chr2:179577592;179577591;179577590
N2A	7810	23653;23654;23655	chr2:178712865;178712864;178712863	chr2:179577592;179577591;179577590
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-76
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.2081
• 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	0.046	N	0.226	0.077	0.17258766438	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	0.7439	likely_pathogenic	0.7802	pathogenic	-0.9	Destabilizing	0.953	D	0.529	neutral	None	None	None	None	N
K/C	0.7973	likely_pathogenic	0.8097	pathogenic	-0.902	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
K/D	0.9301	likely_pathogenic	0.9432	pathogenic	0.298	Stabilizing	0.993	D	0.725	prob.delet.	None	None	None	None	N
K/E	0.4865	ambiguous	0.5299	ambiguous	0.417	Stabilizing	0.939	D	0.451	neutral	D	0.53553969	None	None	N
K/F	0.8679	likely_pathogenic	0.8681	pathogenic	-0.815	Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
K/G	0.8623	likely_pathogenic	0.8768	pathogenic	-1.23	Destabilizing	0.993	D	0.707	prob.neutral	None	None	None	None	N
K/H	0.3954	ambiguous	0.3992	ambiguous	-1.56	Destabilizing	0.998	D	0.761	deleterious	None	None	None	None	N
K/I	0.5661	likely_pathogenic	0.6277	pathogenic	-0.05	Destabilizing	0.991	D	0.807	deleterious	N	0.511395047	None	None	N
K/L	0.5358	ambiguous	0.5809	pathogenic	-0.05	Destabilizing	0.986	D	0.707	prob.neutral	None	None	None	None	N
K/M	0.4288	ambiguous	0.476	ambiguous	-0.132	Destabilizing	0.999	D	0.75	deleterious	None	None	None	None	N
K/N	0.8203	likely_pathogenic	0.8472	pathogenic	-0.355	Destabilizing	0.982	D	0.609	neutral	N	0.503192294	None	None	N
K/P	0.9776	likely_pathogenic	0.9795	pathogenic	-0.306	Destabilizing	0.998	D	0.75	deleterious	None	None	None	None	N
K/Q	0.2181	likely_benign	0.2299	benign	-0.42	Destabilizing	0.982	D	0.593	neutral	N	0.498570711	None	None	N
K/R	0.0707	likely_benign	0.0707	benign	-0.433	Destabilizing	0.046	N	0.226	neutral	N	0.449960079	None	None	N
K/S	0.7888	likely_pathogenic	0.8167	pathogenic	-1.19	Destabilizing	0.953	D	0.539	neutral	None	None	None	None	N
K/T	0.6001	likely_pathogenic	0.662	pathogenic	-0.851	Destabilizing	0.991	D	0.695	prob.neutral	D	0.535032711	None	None	N
K/V	0.5851	likely_pathogenic	0.6445	pathogenic	-0.306	Destabilizing	0.993	D	0.749	deleterious	None	None	None	None	N
K/W	0.7854	likely_pathogenic	0.783	pathogenic	-0.614	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
K/Y	0.7206	likely_pathogenic	0.7308	pathogenic	-0.307	Destabilizing	0.998	D	0.799	deleterious	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.