TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24380	73363;73364;73365	chr2:178572994;178572993;178572992	chr2:179437721;179437720;179437719
N2AB	22739	68440;68441;68442	chr2:178572994;178572993;178572992	chr2:179437721;179437720;179437719
N2A	21812	65659;65660;65661	chr2:178572994;178572993;178572992	chr2:179437721;179437720;179437719
N2B	15315	46168;46169;46170	chr2:178572994;178572993;178572992	chr2:179437721;179437720;179437719
Novex-1	15440	46543;46544;46545	chr2:178572994;178572993;178572992	chr2:179437721;179437720;179437719
Novex-2	15507	46744;46745;46746	chr2:178572994;178572993;178572992	chr2:179437721;179437720;179437719
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-65
• Domain position: 58
• Structural Position: 83
• Q(SASA): 0.8312
• 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	0.407	0.801	N	0.467	0.15	0.18274738541	gnomAD-4.0.0	2.73793E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.63897E-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	0.2718	likely_benign	0.3251	benign	0.015	Stabilizing	0.688	D	0.436	neutral	None	None	None	None	N
K/C	0.614	likely_pathogenic	0.6627	pathogenic	-0.406	Destabilizing	0.998	D	0.517	neutral	None	None	None	None	N
K/D	0.5815	likely_pathogenic	0.6326	pathogenic	0.112	Stabilizing	0.915	D	0.535	neutral	None	None	None	None	N
K/E	0.1929	likely_benign	0.2274	benign	0.112	Stabilizing	0.801	D	0.467	neutral	N	0.448935785	None	None	N
K/F	0.6964	likely_pathogenic	0.729	pathogenic	-0.291	Destabilizing	0.949	D	0.545	neutral	None	None	None	None	N
K/G	0.4007	ambiguous	0.462	ambiguous	-0.137	Destabilizing	0.915	D	0.533	neutral	None	None	None	None	N
K/H	0.2583	likely_benign	0.2945	benign	-0.291	Destabilizing	0.974	D	0.537	neutral	None	None	None	None	N
K/I	0.3086	likely_benign	0.3402	ambiguous	0.329	Stabilizing	0.728	D	0.538	neutral	None	None	None	None	N
K/L	0.2645	likely_benign	0.295	benign	0.329	Stabilizing	0.016	N	0.347	neutral	None	None	None	None	N
K/M	0.2065	likely_benign	0.2353	benign	0.015	Stabilizing	0.934	D	0.542	neutral	N	0.514795418	None	None	N
K/N	0.4062	ambiguous	0.4523	ambiguous	0.105	Stabilizing	0.801	D	0.523	neutral	N	0.405953012	None	None	N
K/P	0.4015	ambiguous	0.4748	ambiguous	0.25	Stabilizing	0.991	D	0.556	neutral	None	None	None	None	N
K/Q	0.1215	likely_benign	0.138	benign	-0.019	Destabilizing	0.934	D	0.541	neutral	N	0.411302903	None	None	N
K/R	0.0761	likely_benign	0.0799	benign	-0.026	Destabilizing	0.012	N	0.249	neutral	N	0.415343286	None	None	N
K/S	0.373	ambiguous	0.4295	ambiguous	-0.353	Destabilizing	0.728	D	0.46	neutral	None	None	None	None	N
K/T	0.145	likely_benign	0.1754	benign	-0.215	Destabilizing	0.022	N	0.246	neutral	N	0.416668651	None	None	N
K/V	0.2694	likely_benign	0.3019	benign	0.25	Stabilizing	0.728	D	0.503	neutral	None	None	None	None	N
K/W	0.6999	likely_pathogenic	0.745	pathogenic	-0.356	Destabilizing	0.998	D	0.521	neutral	None	None	None	None	N
K/Y	0.582	likely_pathogenic	0.6274	pathogenic	0.012	Stabilizing	0.991	D	0.567	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.