TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7691	23296;23297;23298	chr2:178720948;178720947;178720946	chr2:179585675;179585674;179585673
N2AB	7374	22345;22346;22347	chr2:178720948;178720947;178720946	chr2:179585675;179585674;179585673
N2A	6447	19564;19565;19566	chr2:178720948;178720947;178720946	chr2:179585675;179585674;179585673
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-61
• Domain position: 84
• Structural Position: 168
• Q(SASA): 0.2688
• 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
S/N	None	None	0.161	N	0.479	0.172	0.290222751274	gnomAD-4.0.0	3.26339E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.9234E-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
S/A	0.1134	likely_benign	0.1263	benign	-0.589	Destabilizing	0.032	N	0.421	neutral	None	None	None	None	N
S/C	0.2471	likely_benign	0.2774	benign	-0.309	Destabilizing	0.978	D	0.724	prob.delet.	N	0.514018162	None	None	N
S/D	0.5803	likely_pathogenic	0.7609	pathogenic	0.064	Stabilizing	0.685	D	0.491	neutral	None	None	None	None	N
S/E	0.6665	likely_pathogenic	0.8045	pathogenic	0.024	Stabilizing	0.752	D	0.484	neutral	None	None	None	None	N
S/F	0.2244	likely_benign	0.2867	benign	-0.879	Destabilizing	0.983	D	0.771	deleterious	None	None	None	None	N
S/G	0.1505	likely_benign	0.2015	benign	-0.793	Destabilizing	0.752	D	0.455	neutral	D	0.524778583	None	None	N
S/H	0.35	ambiguous	0.5173	ambiguous	-1.209	Destabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	N
S/I	0.195	likely_benign	0.2763	benign	-0.164	Destabilizing	0.915	D	0.749	deleterious	N	0.494748592	None	None	N
S/K	0.6604	likely_pathogenic	0.8672	pathogenic	-0.655	Destabilizing	0.89	D	0.482	neutral	None	None	None	None	N
S/L	0.1492	likely_benign	0.1883	benign	-0.164	Destabilizing	0.802	D	0.609	neutral	None	None	None	None	N
S/M	0.2814	likely_benign	0.3551	ambiguous	0.033	Stabilizing	0.995	D	0.722	prob.delet.	None	None	None	None	N
S/N	0.175	likely_benign	0.2874	benign	-0.402	Destabilizing	0.161	N	0.479	neutral	N	0.492342282	None	None	N
S/P	0.8771	likely_pathogenic	0.9143	pathogenic	-0.273	Destabilizing	0.939	D	0.743	deleterious	None	None	None	None	N
S/Q	0.5259	ambiguous	0.6961	pathogenic	-0.564	Destabilizing	0.983	D	0.639	neutral	None	None	None	None	N
S/R	0.5017	ambiguous	0.7548	pathogenic	-0.486	Destabilizing	0.955	D	0.751	deleterious	N	0.516359295	None	None	N
S/T	0.1035	likely_benign	0.1264	benign	-0.471	Destabilizing	0.001	N	0.357	neutral	N	0.494479726	None	None	N
S/V	0.216	likely_benign	0.2794	benign	-0.273	Destabilizing	0.842	D	0.682	prob.neutral	None	None	None	None	N
S/W	0.4465	ambiguous	0.5655	pathogenic	-0.874	Destabilizing	0.998	D	0.751	deleterious	None	None	None	None	N
S/Y	0.2259	likely_benign	0.3116	benign	-0.622	Destabilizing	0.983	D	0.768	deleterious	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.