TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28635	86128;86129;86130	chr2:178560229;178560228;178560227	chr2:179424956;179424955;179424954
N2AB	26994	81205;81206;81207	chr2:178560229;178560228;178560227	chr2:179424956;179424955;179424954
N2A	26067	78424;78425;78426	chr2:178560229;178560228;178560227	chr2:179424956;179424955;179424954
N2B	19570	58933;58934;58935	chr2:178560229;178560228;178560227	chr2:179424956;179424955;179424954
Novex-1	19695	59308;59309;59310	chr2:178560229;178560228;178560227	chr2:179424956;179424955;179424954
Novex-2	19762	59509;59510;59511	chr2:178560229;178560228;178560227	chr2:179424956;179424955;179424954
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-96
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.7225
• 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/I	rs2154158514	None	0.801	N	0.501	0.126	0.422762650823	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/I	rs2154158514	None	0.801	N	0.501	0.126	0.422762650823	gnomAD-4.0.0	6.56823E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.47016E-05	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	0.0933	likely_benign	0.0971	benign	-1.005	Destabilizing	0.002	N	0.19	neutral	None	None	None	None	I
L/C	0.2717	likely_benign	0.3002	benign	-0.732	Destabilizing	0.998	D	0.514	neutral	None	None	None	None	I
L/D	0.2685	likely_benign	0.2882	benign	-0.13	Destabilizing	0.974	D	0.538	neutral	None	None	None	None	I
L/E	0.1407	likely_benign	0.138	benign	-0.171	Destabilizing	0.842	D	0.557	neutral	None	None	None	None	I
L/F	0.0948	likely_benign	0.0963	benign	-0.754	Destabilizing	0.989	D	0.492	neutral	N	0.4752481	None	None	I
L/G	0.2215	likely_benign	0.2327	benign	-1.234	Destabilizing	0.728	D	0.533	neutral	None	None	None	None	I
L/H	0.1163	likely_benign	0.1211	benign	-0.332	Destabilizing	0.997	D	0.513	neutral	N	0.458835852	None	None	I
L/I	0.0846	likely_benign	0.0882	benign	-0.492	Destabilizing	0.801	D	0.501	neutral	N	0.466263257	None	None	I
L/K	0.1231	likely_benign	0.1255	benign	-0.491	Destabilizing	0.067	N	0.33	neutral	None	None	None	None	I
L/M	0.0919	likely_benign	0.092	benign	-0.547	Destabilizing	0.991	D	0.511	neutral	None	None	None	None	I
L/N	0.1636	likely_benign	0.1784	benign	-0.334	Destabilizing	0.974	D	0.522	neutral	None	None	None	None	I
L/P	0.0753	likely_benign	0.0733	benign	-0.63	Destabilizing	0.966	D	0.539	neutral	N	0.38146836	None	None	I
L/Q	0.0813	likely_benign	0.0817	benign	-0.497	Destabilizing	0.949	D	0.524	neutral	None	None	None	None	I
L/R	0.114	likely_benign	0.1122	benign	0.053	Stabilizing	0.876	D	0.533	neutral	N	0.398883472	None	None	I
L/S	0.0958	likely_benign	0.1018	benign	-0.902	Destabilizing	0.728	D	0.491	neutral	None	None	None	None	I
L/T	0.1088	likely_benign	0.1168	benign	-0.821	Destabilizing	0.842	D	0.5	neutral	None	None	None	None	I
L/V	0.0746	likely_benign	0.0765	benign	-0.63	Destabilizing	0.454	N	0.488	neutral	N	0.423280484	None	None	I
L/W	0.1672	likely_benign	0.1774	benign	-0.751	Destabilizing	0.998	D	0.629	neutral	None	None	None	None	I
L/Y	0.1715	likely_benign	0.1828	benign	-0.527	Destabilizing	0.991	D	0.523	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.