TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21585	64978;64979;64980	chr2:178584888;178584887;178584886	chr2:179449615;179449614;179449613
N2AB	19944	60055;60056;60057	chr2:178584888;178584887;178584886	chr2:179449615;179449614;179449613
N2A	19017	57274;57275;57276	chr2:178584888;178584887;178584886	chr2:179449615;179449614;179449613
N2B	12520	37783;37784;37785	chr2:178584888;178584887;178584886	chr2:179449615;179449614;179449613
Novex-1	12645	38158;38159;38160	chr2:178584888;178584887;178584886	chr2:179449615;179449614;179449613
Novex-2	12712	38359;38360;38361	chr2:178584888;178584887;178584886	chr2:179449615;179449614;179449613
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-44
• Domain position: 27
• Structural Position: 28
• Q(SASA): 0.5991
• 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
L/M	rs772957708	-0.471	0.996	N	0.321	0.254	0.548103985532	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	6.48E-05	0	None	0	0	None	0	None	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
L/A	0.1028	likely_benign	0.0888	benign	-0.578	Destabilizing	0.17	N	0.18	neutral	None	None	None	None	I
L/C	0.468	ambiguous	0.4015	ambiguous	-0.669	Destabilizing	0.999	D	0.312	neutral	None	None	None	None	I
L/D	0.3694	ambiguous	0.3007	benign	-0.385	Destabilizing	0.982	D	0.383	neutral	None	None	None	None	I
L/E	0.1546	likely_benign	0.1339	benign	-0.484	Destabilizing	0.884	D	0.369	neutral	None	None	None	None	I
L/F	0.1557	likely_benign	0.1257	benign	-0.633	Destabilizing	0.997	D	0.295	neutral	None	None	None	None	I
L/G	0.3181	likely_benign	0.2734	benign	-0.721	Destabilizing	0.884	D	0.361	neutral	None	None	None	None	I
L/H	0.1799	likely_benign	0.1538	benign	0.011	Stabilizing	0.991	D	0.359	neutral	None	None	None	None	I
L/I	0.0917	likely_benign	0.0802	benign	-0.327	Destabilizing	0.969	D	0.315	neutral	None	None	None	None	I
L/K	0.1329	likely_benign	0.1208	benign	-0.395	Destabilizing	0.884	D	0.337	neutral	None	None	None	None	I
L/M	0.0928	likely_benign	0.0845	benign	-0.464	Destabilizing	0.996	D	0.321	neutral	N	0.519847026	None	None	I
L/N	0.218	likely_benign	0.1663	benign	-0.209	Destabilizing	0.991	D	0.383	neutral	None	None	None	None	I
L/P	0.1763	likely_benign	0.1744	benign	-0.379	Destabilizing	0.988	D	0.402	neutral	N	0.493871146	None	None	I
L/Q	0.0883	likely_benign	0.0828	benign	-0.449	Destabilizing	0.31	N	0.202	neutral	N	0.465377823	None	None	I
L/R	0.1392	likely_benign	0.1318	benign	0.191	Stabilizing	0.035	N	0.232	neutral	N	0.491177557	None	None	I
L/S	0.1312	likely_benign	0.1031	benign	-0.604	Destabilizing	0.884	D	0.368	neutral	None	None	None	None	I
L/T	0.1111	likely_benign	0.0897	benign	-0.598	Destabilizing	0.939	D	0.312	neutral	None	None	None	None	I
L/V	0.0762	likely_benign	0.0708	benign	-0.379	Destabilizing	0.92	D	0.318	neutral	N	0.489697477	None	None	I
L/W	0.2701	likely_benign	0.2514	benign	-0.64	Destabilizing	0.999	D	0.421	neutral	None	None	None	None	I
L/Y	0.3139	likely_benign	0.257	benign	-0.402	Destabilizing	0.997	D	0.31	neutral	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.