TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17825	53698;53699;53700	chr2:178607129;178607128;178607127	chr2:179471856;179471855;179471854
N2AB	16184	48775;48776;48777	chr2:178607129;178607128;178607127	chr2:179471856;179471855;179471854
N2A	15257	45994;45995;45996	chr2:178607129;178607128;178607127	chr2:179471856;179471855;179471854
N2B	8760	26503;26504;26505	chr2:178607129;178607128;178607127	chr2:179471856;179471855;179471854
Novex-1	8885	26878;26879;26880	chr2:178607129;178607128;178607127	chr2:179471856;179471855;179471854
Novex-2	8952	27079;27080;27081	chr2:178607129;178607128;178607127	chr2:179471856;179471855;179471854
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: Fn3-17
• Domain position: 62
• Structural Position: 94
• Q(SASA): 0.5698
• 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/I	rs2055078355	None	0.454	N	0.346	0.21	0.463843524616	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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	0.1503	likely_benign	0.2042	benign	-0.6	Destabilizing	0.454	N	0.324	neutral	N	0.48190585	None	None	N
T/C	0.5657	likely_pathogenic	0.6636	pathogenic	-0.377	Destabilizing	0.998	D	0.419	neutral	None	None	None	None	N
T/D	0.8032	likely_pathogenic	0.8593	pathogenic	0.241	Stabilizing	0.915	D	0.387	neutral	None	None	None	None	N
T/E	0.692	likely_pathogenic	0.7549	pathogenic	0.212	Stabilizing	0.728	D	0.348	neutral	None	None	None	None	N
T/F	0.5525	ambiguous	0.6304	pathogenic	-0.85	Destabilizing	0.974	D	0.49	neutral	None	None	None	None	N
T/G	0.3866	ambiguous	0.4766	ambiguous	-0.806	Destabilizing	0.915	D	0.445	neutral	None	None	None	None	N
T/H	0.5271	ambiguous	0.6517	pathogenic	-1.005	Destabilizing	0.993	D	0.469	neutral	None	None	None	None	N
T/I	0.3198	likely_benign	0.4087	ambiguous	-0.16	Destabilizing	0.454	N	0.346	neutral	N	0.476425348	None	None	N
T/K	0.4994	ambiguous	0.6259	pathogenic	-0.508	Destabilizing	0.669	D	0.383	neutral	N	0.488660114	None	None	N
T/L	0.1704	likely_benign	0.2523	benign	-0.16	Destabilizing	0.525	D	0.385	neutral	None	None	None	None	N
T/M	0.1638	likely_benign	0.2051	benign	-0.023	Destabilizing	0.974	D	0.424	neutral	None	None	None	None	N
T/N	0.2848	likely_benign	0.3897	ambiguous	-0.394	Destabilizing	0.974	D	0.353	neutral	None	None	None	None	N
T/P	0.1639	likely_benign	0.2736	benign	-0.275	Destabilizing	0.989	D	0.416	neutral	N	0.511979691	None	None	N
T/Q	0.4163	ambiguous	0.5257	ambiguous	-0.539	Destabilizing	0.325	N	0.253	neutral	None	None	None	None	N
T/R	0.454	ambiguous	0.5734	pathogenic	-0.259	Destabilizing	0.934	D	0.415	neutral	N	0.511632974	None	None	N
T/S	0.2055	likely_benign	0.2713	benign	-0.678	Destabilizing	0.801	D	0.297	neutral	N	0.477018968	None	None	N
T/V	0.1975	likely_benign	0.246	benign	-0.275	Destabilizing	0.007	N	0.125	neutral	None	None	None	None	N
T/W	0.8177	likely_pathogenic	0.876	pathogenic	-0.82	Destabilizing	0.998	D	0.522	neutral	None	None	None	None	N
T/Y	0.5821	likely_pathogenic	0.6904	pathogenic	-0.564	Destabilizing	0.991	D	0.489	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.