TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16700	50323;50324;50325	chr2:178612427;178612426;178612425	chr2:179477154;179477153;179477152
N2AB	15059	45400;45401;45402	chr2:178612427;178612426;178612425	chr2:179477154;179477153;179477152
N2A	14132	42619;42620;42621	chr2:178612427;178612426;178612425	chr2:179477154;179477153;179477152
N2B	7635	23128;23129;23130	chr2:178612427;178612426;178612425	chr2:179477154;179477153;179477152
Novex-1	7760	23503;23504;23505	chr2:178612427;178612426;178612425	chr2:179477154;179477153;179477152
Novex-2	7827	23704;23705;23706	chr2:178612427;178612426;178612425	chr2:179477154;179477153;179477152
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: Fn3-9
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.4031
• 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	None	None	0.012	N	0.161	0.074	0.126345400529	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.1317	likely_benign	0.1309	benign	-0.642	Destabilizing	0.012	N	0.161	neutral	N	0.445109725	None	None	N
T/C	0.7057	likely_pathogenic	0.7435	pathogenic	-0.42	Destabilizing	0.996	D	0.614	neutral	None	None	None	None	N
T/D	0.8977	likely_pathogenic	0.9102	pathogenic	-0.352	Destabilizing	0.742	D	0.523	neutral	None	None	None	None	N
T/E	0.7797	likely_pathogenic	0.812	pathogenic	-0.367	Destabilizing	0.742	D	0.521	neutral	None	None	None	None	N
T/F	0.6953	likely_pathogenic	0.7373	pathogenic	-0.693	Destabilizing	0.953	D	0.673	neutral	None	None	None	None	N
T/G	0.6898	likely_pathogenic	0.6408	pathogenic	-0.891	Destabilizing	0.373	N	0.513	neutral	None	None	None	None	N
T/H	0.7691	likely_pathogenic	0.7779	pathogenic	-1.168	Destabilizing	0.996	D	0.662	neutral	None	None	None	None	N
T/I	0.2927	likely_benign	0.3367	benign	-0.074	Destabilizing	0.939	D	0.553	neutral	N	0.485759245	None	None	N
T/K	0.6569	likely_pathogenic	0.7261	pathogenic	-0.852	Destabilizing	0.684	D	0.519	neutral	N	0.415893674	None	None	N
T/L	0.1897	likely_benign	0.2068	benign	-0.074	Destabilizing	0.742	D	0.473	neutral	None	None	None	None	N
T/M	0.1453	likely_benign	0.1408	benign	0.155	Stabilizing	0.996	D	0.62	neutral	None	None	None	None	N
T/N	0.381	ambiguous	0.3665	ambiguous	-0.717	Destabilizing	0.742	D	0.441	neutral	None	None	None	None	N
T/P	0.2503	likely_benign	0.26	benign	-0.231	Destabilizing	0.939	D	0.568	neutral	N	0.474748367	None	None	N
T/Q	0.5922	likely_pathogenic	0.5997	pathogenic	-0.885	Destabilizing	0.91	D	0.604	neutral	None	None	None	None	N
T/R	0.6552	likely_pathogenic	0.7318	pathogenic	-0.564	Destabilizing	0.884	D	0.573	neutral	N	0.466096417	None	None	N
T/S	0.3345	likely_benign	0.313	benign	-0.933	Destabilizing	0.028	N	0.189	neutral	N	0.469199012	None	None	N
T/V	0.1796	likely_benign	0.196	benign	-0.231	Destabilizing	0.742	D	0.38	neutral	None	None	None	None	N
T/W	0.9398	likely_pathogenic	0.9528	pathogenic	-0.668	Destabilizing	0.996	D	0.707	prob.neutral	None	None	None	None	N
T/Y	0.7716	likely_pathogenic	0.8163	pathogenic	-0.449	Destabilizing	0.984	D	0.671	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.