TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5876	17851;17852;17853	chr2:178731039;178731038;178731037	chr2:179595766;179595765;179595764
N2AB	5559	16900;16901;16902	chr2:178731039;178731038;178731037	chr2:179595766;179595765;179595764
N2A	4632	14119;14120;14121	chr2:178731039;178731038;178731037	chr2:179595766;179595765;179595764
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-42
• Domain position: 54
• Structural Position: 134
• Q(SASA): 0.3145
• 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
T/A	rs1376088246	None	0.09	N	0.413	0.154	0.263140351381	gnomAD-4.0.0	1.36851E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79906E-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
T/A	0.0765	likely_benign	0.0793	benign	-0.611	Destabilizing	0.09	N	0.413	neutral	N	0.488015114	None	None	N
T/C	0.4553	ambiguous	0.4654	ambiguous	-0.401	Destabilizing	0.981	D	0.577	neutral	None	None	None	None	N
T/D	0.2629	likely_benign	0.2837	benign	0.369	Stabilizing	0.241	N	0.505	neutral	None	None	None	None	N
T/E	0.2244	likely_benign	0.2453	benign	0.342	Stabilizing	0.241	N	0.479	neutral	None	None	None	None	N
T/F	0.2429	likely_benign	0.2364	benign	-0.854	Destabilizing	0.932	D	0.663	neutral	None	None	None	None	N
T/G	0.2032	likely_benign	0.2023	benign	-0.815	Destabilizing	0.241	N	0.569	neutral	None	None	None	None	N
T/H	0.1916	likely_benign	0.2025	benign	-1.077	Destabilizing	0.818	D	0.651	neutral	None	None	None	None	N
T/I	0.2226	likely_benign	0.2367	benign	-0.175	Destabilizing	0.773	D	0.592	neutral	N	0.492467186	None	None	N
T/K	0.1271	likely_benign	0.1402	benign	-0.45	Destabilizing	0.193	N	0.47	neutral	N	0.462503381	None	None	N
T/L	0.1151	likely_benign	0.1183	benign	-0.175	Destabilizing	0.388	N	0.494	neutral	None	None	None	None	N
T/M	0.0878	likely_benign	0.0882	benign	-0.043	Destabilizing	0.981	D	0.569	neutral	None	None	None	None	N
T/N	0.093	likely_benign	0.0978	benign	-0.364	Destabilizing	0.002	N	0.166	neutral	None	None	None	None	N
T/P	0.2708	likely_benign	0.2972	benign	-0.289	Destabilizing	0.773	D	0.591	neutral	N	0.500139049	None	None	N
T/Q	0.1651	likely_benign	0.181	benign	-0.512	Destabilizing	0.69	D	0.583	neutral	None	None	None	None	N
T/R	0.1051	likely_benign	0.1183	benign	-0.257	Destabilizing	0.003	N	0.287	neutral	N	0.482572009	None	None	N
T/S	0.0973	likely_benign	0.0934	benign	-0.662	Destabilizing	0.018	N	0.213	neutral	N	0.444264337	None	None	N
T/V	0.1747	likely_benign	0.176	benign	-0.289	Destabilizing	0.388	N	0.466	neutral	None	None	None	None	N
T/W	0.5472	ambiguous	0.5499	ambiguous	-0.807	Destabilizing	0.981	D	0.702	prob.neutral	None	None	None	None	N
T/Y	0.2393	likely_benign	0.244	benign	-0.549	Destabilizing	0.932	D	0.662	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.