TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30273	91042;91043;91044	chr2:178552083;178552082;178552081	chr2:179416810;179416809;179416808
N2AB	28632	86119;86120;86121	chr2:178552083;178552082;178552081	chr2:179416810;179416809;179416808
N2A	27705	83338;83339;83340	chr2:178552083;178552082;178552081	chr2:179416810;179416809;179416808
N2B	21208	63847;63848;63849	chr2:178552083;178552082;178552081	chr2:179416810;179416809;179416808
Novex-1	21333	64222;64223;64224	chr2:178552083;178552082;178552081	chr2:179416810;179416809;179416808
Novex-2	21400	64423;64424;64425	chr2:178552083;178552082;178552081	chr2:179416810;179416809;179416808
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: Fn3-108
• Domain position: 50
• Structural Position: 66
• Q(SASA): 0.582
• 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	rs1307577297	None	1.0	N	0.729	0.323	0.228597637076	gnomAD-4.0.0	3.18286E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.7171E-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	0.8129	likely_pathogenic	0.6423	pathogenic	-0.372	Destabilizing	0.999	D	0.69	prob.neutral	None	None	None	None	N
K/C	0.8963	likely_pathogenic	0.8087	pathogenic	-0.443	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
K/D	0.9076	likely_pathogenic	0.8081	pathogenic	-0.076	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
K/E	0.557	ambiguous	0.3523	ambiguous	0.034	Stabilizing	0.999	D	0.659	neutral	N	0.438828726	None	None	N
K/F	0.9504	likely_pathogenic	0.9042	pathogenic	0.03	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
K/G	0.8742	likely_pathogenic	0.7658	pathogenic	-0.725	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
K/H	0.521	ambiguous	0.4043	ambiguous	-0.915	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
K/I	0.6654	likely_pathogenic	0.5054	ambiguous	0.537	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
K/L	0.6993	likely_pathogenic	0.5554	ambiguous	0.537	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
K/M	0.5414	ambiguous	0.3771	ambiguous	0.167	Stabilizing	1.0	D	0.696	prob.neutral	N	0.472114581	None	None	N
K/N	0.7887	likely_pathogenic	0.6256	pathogenic	-0.363	Destabilizing	1.0	D	0.729	prob.delet.	N	0.48225143	None	None	N
K/P	0.9821	likely_pathogenic	0.9682	pathogenic	0.264	Stabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
K/Q	0.2601	likely_benign	0.1762	benign	-0.365	Destabilizing	1.0	D	0.706	prob.neutral	N	0.375950684	None	None	N
K/R	0.1054	likely_benign	0.0972	benign	-0.542	Destabilizing	0.999	D	0.613	neutral	N	0.444330547	None	None	N
K/S	0.8362	likely_pathogenic	0.6847	pathogenic	-0.914	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
K/T	0.5457	ambiguous	0.35	ambiguous	-0.608	Destabilizing	1.0	D	0.717	prob.delet.	N	0.429246451	None	None	N
K/V	0.6105	likely_pathogenic	0.453	ambiguous	0.264	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
K/W	0.9384	likely_pathogenic	0.8901	pathogenic	0.087	Stabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
K/Y	0.8762	likely_pathogenic	0.7944	pathogenic	0.348	Stabilizing	1.0	D	0.716	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.