TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25172	75739;75740;75741	chr2:178570618;178570617;178570616	chr2:179435345;179435344;179435343
N2AB	23531	70816;70817;70818	chr2:178570618;178570617;178570616	chr2:179435345;179435344;179435343
N2A	22604	68035;68036;68037	chr2:178570618;178570617;178570616	chr2:179435345;179435344;179435343
N2B	16107	48544;48545;48546	chr2:178570618;178570617;178570616	chr2:179435345;179435344;179435343
Novex-1	16232	48919;48920;48921	chr2:178570618;178570617;178570616	chr2:179435345;179435344;179435343
Novex-2	16299	49120;49121;49122	chr2:178570618;178570617;178570616	chr2:179435345;179435344;179435343
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-134
• Domain position: 62
• Structural Position: 141
• Q(SASA): 0.6112
• 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/N	None	None	0.999	N	0.661	0.292	0.19670166235	gnomAD-4.0.0	1.59193E-06	None	None	None	None	N	None	0	2.28718E-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	0.618	likely_pathogenic	0.6393	pathogenic	-0.246	Destabilizing	0.998	D	0.602	neutral	None	None	None	None	N
K/C	0.8043	likely_pathogenic	0.8383	pathogenic	-0.307	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
K/D	0.8408	likely_pathogenic	0.8581	pathogenic	0.005	Stabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
K/E	0.4111	ambiguous	0.4483	ambiguous	0.022	Stabilizing	0.996	D	0.551	neutral	D	0.528440371	None	None	N
K/F	0.8916	likely_pathogenic	0.9112	pathogenic	-0.492	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
K/G	0.7193	likely_pathogenic	0.7305	pathogenic	-0.485	Destabilizing	1.0	D	0.59	neutral	None	None	None	None	N
K/H	0.438	ambiguous	0.4571	ambiguous	-0.967	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
K/I	0.5737	likely_pathogenic	0.6106	pathogenic	0.315	Stabilizing	1.0	D	0.7	prob.neutral	N	0.49400135	None	None	N
K/L	0.5848	likely_pathogenic	0.6252	pathogenic	0.315	Stabilizing	1.0	D	0.59	neutral	None	None	None	None	N
K/M	0.4155	ambiguous	0.447	ambiguous	0.426	Stabilizing	1.0	D	0.649	neutral	None	None	None	None	N
K/N	0.7129	likely_pathogenic	0.7232	pathogenic	0.134	Stabilizing	0.999	D	0.661	neutral	N	0.484580374	None	None	N
K/P	0.8838	likely_pathogenic	0.8933	pathogenic	0.157	Stabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
K/Q	0.2472	likely_benign	0.2504	benign	-0.165	Destabilizing	0.999	D	0.653	neutral	N	0.48699623	None	None	N
K/R	0.0913	likely_benign	0.0915	benign	-0.082	Destabilizing	0.884	D	0.299	neutral	N	0.474645959	None	None	N
K/S	0.6829	likely_pathogenic	0.6999	pathogenic	-0.483	Destabilizing	0.998	D	0.606	neutral	None	None	None	None	N
K/T	0.3409	ambiguous	0.3631	ambiguous	-0.303	Destabilizing	0.999	D	0.659	neutral	D	0.527517651	None	None	N
K/V	0.5525	ambiguous	0.588	pathogenic	0.157	Stabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
K/W	0.8101	likely_pathogenic	0.8487	pathogenic	-0.387	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
K/Y	0.8004	likely_pathogenic	0.8313	pathogenic	-0.01	Destabilizing	1.0	D	0.674	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.