TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27018	81277;81278;81279	chr2:178565080;178565079;178565078	chr2:179429807;179429806;179429805
N2AB	25377	76354;76355;76356	chr2:178565080;178565079;178565078	chr2:179429807;179429806;179429805
N2A	24450	73573;73574;73575	chr2:178565080;178565079;178565078	chr2:179429807;179429806;179429805
N2B	17953	54082;54083;54084	chr2:178565080;178565079;178565078	chr2:179429807;179429806;179429805
Novex-1	18078	54457;54458;54459	chr2:178565080;178565079;178565078	chr2:179429807;179429806;179429805
Novex-2	18145	54658;54659;54660	chr2:178565080;178565079;178565078	chr2:179429807;179429806;179429805
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-84
• Domain position: 47
• Structural Position: 63
• Q(SASA): 0.7946
• 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/S	None	None	0.958	N	0.425	0.265	0.185906805712	gnomAD-4.0.0	1.59162E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85917E-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	0.1213	likely_benign	0.1085	benign	-0.322	Destabilizing	0.825	D	0.445	neutral	N	0.491852348	None	None	N
T/C	0.8127	likely_pathogenic	0.7752	pathogenic	-0.301	Destabilizing	1.0	D	0.548	neutral	None	None	None	None	N
T/D	0.785	likely_pathogenic	0.7862	pathogenic	0.164	Stabilizing	0.991	D	0.485	neutral	None	None	None	None	N
T/E	0.7115	likely_pathogenic	0.7156	pathogenic	0.081	Stabilizing	0.995	D	0.491	neutral	None	None	None	None	N
T/F	0.7378	likely_pathogenic	0.7261	pathogenic	-0.926	Destabilizing	0.998	D	0.547	neutral	None	None	None	None	N
T/G	0.4323	ambiguous	0.3857	ambiguous	-0.416	Destabilizing	0.086	N	0.361	neutral	None	None	None	None	N
T/H	0.7184	likely_pathogenic	0.6821	pathogenic	-0.619	Destabilizing	1.0	D	0.555	neutral	None	None	None	None	N
T/I	0.4836	ambiguous	0.5157	ambiguous	-0.197	Destabilizing	0.998	D	0.496	neutral	N	0.476737609	None	None	N
T/K	0.6018	likely_pathogenic	0.5891	pathogenic	-0.296	Destabilizing	0.991	D	0.497	neutral	None	None	None	None	N
T/L	0.2276	likely_benign	0.2263	benign	-0.197	Destabilizing	0.984	D	0.446	neutral	None	None	None	None	N
T/M	0.1738	likely_benign	0.1607	benign	-0.132	Destabilizing	1.0	D	0.541	neutral	None	None	None	None	N
T/N	0.3192	likely_benign	0.3054	benign	-0.09	Destabilizing	0.988	D	0.49	neutral	N	0.489657405	None	None	N
T/P	0.289	likely_benign	0.2718	benign	-0.213	Destabilizing	0.998	D	0.494	neutral	N	0.516556004	None	None	N
T/Q	0.5387	ambiguous	0.4938	ambiguous	-0.295	Destabilizing	0.998	D	0.525	neutral	None	None	None	None	N
T/R	0.5734	likely_pathogenic	0.5653	pathogenic	-0.006	Destabilizing	0.995	D	0.502	neutral	None	None	None	None	N
T/S	0.2218	likely_benign	0.2007	benign	-0.284	Destabilizing	0.958	D	0.425	neutral	N	0.454699469	None	None	N
T/V	0.278	likely_benign	0.2827	benign	-0.213	Destabilizing	0.984	D	0.425	neutral	None	None	None	None	N
T/W	0.9492	likely_pathogenic	0.9501	pathogenic	-0.973	Destabilizing	1.0	D	0.613	neutral	None	None	None	None	N
T/Y	0.7763	likely_pathogenic	0.768	pathogenic	-0.667	Destabilizing	0.998	D	0.553	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.