TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27000	81223;81224;81225	chr2:178565134;178565133;178565132	chr2:179429861;179429860;179429859
N2AB	25359	76300;76301;76302	chr2:178565134;178565133;178565132	chr2:179429861;179429860;179429859
N2A	24432	73519;73520;73521	chr2:178565134;178565133;178565132	chr2:179429861;179429860;179429859
N2B	17935	54028;54029;54030	chr2:178565134;178565133;178565132	chr2:179429861;179429860;179429859
Novex-1	18060	54403;54404;54405	chr2:178565134;178565133;178565132	chr2:179429861;179429860;179429859
Novex-2	18127	54604;54605;54606	chr2:178565134;178565133;178565132	chr2:179429861;179429860;179429859
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-84
• Domain position: 29
• Structural Position: 30
• Q(SASA): 0.2594
• 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
T/I	None	None	0.97	N	0.631	0.332	0.36355261348	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1261	likely_benign	0.1198	benign	-1.069	Destabilizing	0.489	N	0.561	neutral	N	0.517326796	None	None	I
T/C	0.6476	likely_pathogenic	0.6158	pathogenic	-0.67	Destabilizing	0.998	D	0.651	neutral	None	None	None	None	I
T/D	0.2656	likely_benign	0.3028	benign	-0.483	Destabilizing	0.019	N	0.237	neutral	None	None	None	None	I
T/E	0.3948	ambiguous	0.3988	ambiguous	-0.433	Destabilizing	0.754	D	0.57	neutral	None	None	None	None	I
T/F	0.49	ambiguous	0.4676	ambiguous	-0.994	Destabilizing	0.993	D	0.697	prob.neutral	None	None	None	None	I
T/G	0.2986	likely_benign	0.3042	benign	-1.377	Destabilizing	0.86	D	0.643	neutral	None	None	None	None	I
T/H	0.391	ambiguous	0.3718	ambiguous	-1.615	Destabilizing	0.998	D	0.685	prob.neutral	None	None	None	None	I
T/I	0.4076	ambiguous	0.3696	ambiguous	-0.319	Destabilizing	0.97	D	0.631	neutral	N	0.476852968	None	None	I
T/K	0.3396	likely_benign	0.3502	ambiguous	-0.775	Destabilizing	0.86	D	0.554	neutral	None	None	None	None	I
T/L	0.1563	likely_benign	0.1434	benign	-0.319	Destabilizing	0.926	D	0.557	neutral	None	None	None	None	I
T/M	0.1499	likely_benign	0.1374	benign	-0.03	Destabilizing	0.998	D	0.642	neutral	None	None	None	None	I
T/N	0.123	likely_benign	0.1296	benign	-0.855	Destabilizing	0.698	D	0.569	neutral	N	0.477904403	None	None	I
T/P	0.2079	likely_benign	0.1835	benign	-0.537	Destabilizing	0.97	D	0.617	neutral	N	0.478548034	None	None	I
T/Q	0.3458	ambiguous	0.338	benign	-0.958	Destabilizing	0.978	D	0.636	neutral	None	None	None	None	I
T/R	0.3127	likely_benign	0.3282	benign	-0.636	Destabilizing	0.978	D	0.635	neutral	None	None	None	None	I
T/S	0.1155	likely_benign	0.1177	benign	-1.171	Destabilizing	0.153	N	0.265	neutral	N	0.484963661	None	None	I
T/V	0.2759	likely_benign	0.2548	benign	-0.537	Destabilizing	0.926	D	0.57	neutral	None	None	None	None	I
T/W	0.8028	likely_pathogenic	0.7818	pathogenic	-0.918	Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	I
T/Y	0.478	ambiguous	0.4476	ambiguous	-0.679	Destabilizing	0.993	D	0.695	prob.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.