TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21650	65173;65174;65175	chr2:178584693;178584692;178584691	chr2:179449420;179449419;179449418
N2AB	20009	60250;60251;60252	chr2:178584693;178584692;178584691	chr2:179449420;179449419;179449418
N2A	19082	57469;57470;57471	chr2:178584693;178584692;178584691	chr2:179449420;179449419;179449418
N2B	12585	37978;37979;37980	chr2:178584693;178584692;178584691	chr2:179449420;179449419;179449418
Novex-1	12710	38353;38354;38355	chr2:178584693;178584692;178584691	chr2:179449420;179449419;179449418
Novex-2	12777	38554;38555;38556	chr2:178584693;178584692;178584691	chr2:179449420;179449419;179449418
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: Fn3-44
• Domain position: 92
• Structural Position: 126
• Q(SASA): 0.8079
• Predicted PPI site: I

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	rs2048550217	None	0.991	N	0.554	0.239	0.251639045875	gnomAD-4.0.0	1.59198E-06	None	None	None	None	I	None	5.66508E-05	0	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	0.2596	likely_benign	0.2612	benign	-0.139	Destabilizing	0.997	D	0.61	neutral	None	None	None	None	I
K/C	0.6227	likely_pathogenic	0.5933	pathogenic	-0.41	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	I
K/D	0.5813	likely_pathogenic	0.5953	pathogenic	-0.028	Destabilizing	0.999	D	0.768	deleterious	None	None	None	None	I
K/E	0.1643	likely_benign	0.171	benign	0.038	Stabilizing	0.991	D	0.554	neutral	N	0.391991998	None	None	I
K/F	0.7808	likely_pathogenic	0.7829	pathogenic	-0.046	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
K/G	0.3962	ambiguous	0.4065	ambiguous	-0.418	Destabilizing	0.999	D	0.61	neutral	None	None	None	None	I
K/H	0.3292	likely_benign	0.3348	benign	-0.593	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
K/I	0.3665	ambiguous	0.3813	ambiguous	0.546	Stabilizing	1.0	D	0.832	deleterious	None	None	None	None	I
K/L	0.3429	ambiguous	0.3496	ambiguous	0.546	Stabilizing	0.999	D	0.61	neutral	None	None	None	None	I
K/M	0.2542	likely_benign	0.2695	benign	0.113	Stabilizing	1.0	D	0.759	deleterious	N	0.453195172	None	None	I
K/N	0.4399	ambiguous	0.4561	ambiguous	-0.154	Destabilizing	0.999	D	0.753	deleterious	N	0.411713909	None	None	I
K/P	0.339	likely_benign	0.3315	benign	0.348	Stabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
K/Q	0.1306	likely_benign	0.1334	benign	-0.21	Destabilizing	0.997	D	0.771	deleterious	N	0.430126312	None	None	I
K/R	0.073	likely_benign	0.0726	benign	-0.259	Destabilizing	0.451	N	0.329	neutral	N	0.408038886	None	None	I
K/S	0.3608	ambiguous	0.3702	ambiguous	-0.64	Destabilizing	0.997	D	0.679	prob.neutral	None	None	None	None	I
K/T	0.1774	likely_benign	0.1863	benign	-0.398	Destabilizing	0.999	D	0.717	prob.delet.	N	0.40844153	None	None	I
K/V	0.2813	likely_benign	0.2918	benign	0.348	Stabilizing	0.999	D	0.751	deleterious	None	None	None	None	I
K/W	0.7986	likely_pathogenic	0.8024	pathogenic	-0.048	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
K/Y	0.6251	likely_pathogenic	0.6321	pathogenic	0.267	Stabilizing	1.0	D	0.796	deleterious	None	None	None	None	I

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.