TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19637	59134;59135;59136	chr2:178593299;178593298;178593297	chr2:179458026;179458025;179458024
N2AB	17996	54211;54212;54213	chr2:178593299;178593298;178593297	chr2:179458026;179458025;179458024
N2A	17069	51430;51431;51432	chr2:178593299;178593298;178593297	chr2:179458026;179458025;179458024
N2B	10572	31939;31940;31941	chr2:178593299;178593298;178593297	chr2:179458026;179458025;179458024
Novex-1	10697	32314;32315;32316	chr2:178593299;178593298;178593297	chr2:179458026;179458025;179458024
Novex-2	10764	32515;32516;32517	chr2:178593299;178593298;178593297	chr2:179458026;179458025;179458024
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: Fn3-30
• Domain position: 59
• Structural Position: 89
• Q(SASA): 0.1315
• 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	rs780393880	-0.675	0.64	N	0.476	0.246	0.176091768786	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
T/S	rs780393880	-0.978	0.103	N	0.499	0.234	0.154104182512	gnomAD-2.1.1	2.81E-05	None	None	None	None	N	None	0	2.03016E-04	None	0	0	None	0	None	0	0	0
T/S	rs780393880	-0.978	0.103	N	0.499	0.234	0.154104182512	gnomAD-4.0.0	1.20034E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31252E-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	0.1101	likely_benign	0.1147	benign	-0.834	Destabilizing	0.64	D	0.476	neutral	N	0.475598747	None	None	N
T/C	0.2916	likely_benign	0.3329	benign	-0.428	Destabilizing	0.999	D	0.603	neutral	None	None	None	None	N
T/D	0.4866	ambiguous	0.5502	ambiguous	-0.519	Destabilizing	0.976	D	0.536	neutral	None	None	None	None	N
T/E	0.3525	ambiguous	0.3877	ambiguous	-0.355	Destabilizing	0.976	D	0.525	neutral	None	None	None	None	N
T/F	0.4254	ambiguous	0.4916	ambiguous	-0.688	Destabilizing	0.988	D	0.659	neutral	None	None	None	None	N
T/G	0.2467	likely_benign	0.2747	benign	-1.216	Destabilizing	0.851	D	0.552	neutral	None	None	None	None	N
T/H	0.3701	ambiguous	0.4087	ambiguous	-1.232	Destabilizing	0.999	D	0.686	prob.neutral	None	None	None	None	N
T/I	0.2562	likely_benign	0.2801	benign	0.147	Stabilizing	0.811	D	0.513	neutral	N	0.515174618	None	None	N
T/K	0.3019	likely_benign	0.2924	benign	-0.213	Destabilizing	0.976	D	0.525	neutral	None	None	None	None	N
T/L	0.0961	likely_benign	0.1057	benign	0.147	Stabilizing	0.851	D	0.512	neutral	None	None	None	None	N
T/M	0.117	likely_benign	0.1226	benign	0.068	Stabilizing	0.988	D	0.594	neutral	None	None	None	None	N
T/N	0.1423	likely_benign	0.1677	benign	-0.761	Destabilizing	0.968	D	0.482	neutral	N	0.516961436	None	None	N
T/P	0.1252	likely_benign	0.1369	benign	-0.148	Destabilizing	0.984	D	0.568	neutral	N	0.480687628	None	None	N
T/Q	0.2482	likely_benign	0.2544	benign	-0.569	Destabilizing	0.988	D	0.589	neutral	None	None	None	None	N
T/R	0.2415	likely_benign	0.2275	benign	-0.343	Destabilizing	0.976	D	0.569	neutral	None	None	None	None	N
T/S	0.1306	likely_benign	0.148	benign	-1.078	Destabilizing	0.103	N	0.499	neutral	N	0.481257059	None	None	N
T/V	0.1636	likely_benign	0.1778	benign	-0.148	Destabilizing	0.132	N	0.317	neutral	None	None	None	None	N
T/W	0.7336	likely_pathogenic	0.7756	pathogenic	-0.805	Destabilizing	0.999	D	0.684	prob.neutral	None	None	None	None	N
T/Y	0.4391	ambiguous	0.5038	ambiguous	-0.41	Destabilizing	0.996	D	0.666	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.