TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31091	93496;93497;93498	chr2:178548355;178548354;178548353	chr2:179413082;179413081;179413080
N2AB	29450	88573;88574;88575	chr2:178548355;178548354;178548353	chr2:179413082;179413081;179413080
N2A	28523	85792;85793;85794	chr2:178548355;178548354;178548353	chr2:179413082;179413081;179413080
N2B	22026	66301;66302;66303	chr2:178548355;178548354;178548353	chr2:179413082;179413081;179413080
Novex-1	22151	66676;66677;66678	chr2:178548355;178548354;178548353	chr2:179413082;179413081;179413080
Novex-2	22218	66877;66878;66879	chr2:178548355;178548354;178548353	chr2:179413082;179413081;179413080
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-114
• Domain position: 76
• Structural Position: 109
• Q(SASA): 0.1343
• 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/F	None	None	0.001	N	0.671	0.275	0.400613892164	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
S/A	0.0756	likely_benign	0.083	benign	-1.113	Destabilizing	0.037	N	0.453	neutral	N	0.476842823	None	None	N
S/C	0.0814	likely_benign	0.0757	benign	-1.031	Destabilizing	0.822	D	0.694	prob.neutral	N	0.501087907	None	None	N
S/D	0.7218	likely_pathogenic	0.7346	pathogenic	-2.063	Highly Destabilizing	0.364	N	0.647	neutral	None	None	None	None	N
S/E	0.6875	likely_pathogenic	0.6989	pathogenic	-1.848	Destabilizing	0.364	N	0.654	neutral	None	None	None	None	N
S/F	0.2199	likely_benign	0.2215	benign	-0.662	Destabilizing	0.001	N	0.671	neutral	N	0.483232865	None	None	N
S/G	0.1215	likely_benign	0.1214	benign	-1.497	Destabilizing	0.191	N	0.572	neutral	None	None	None	None	N
S/H	0.4174	ambiguous	0.3993	ambiguous	-1.701	Destabilizing	0.859	D	0.695	prob.neutral	None	None	None	None	N
S/I	0.2296	likely_benign	0.2411	benign	-0.122	Destabilizing	0.004	N	0.535	neutral	None	None	None	None	N
S/K	0.7276	likely_pathogenic	0.7328	pathogenic	-0.792	Destabilizing	0.22	N	0.654	neutral	None	None	None	None	N
S/L	0.0848	likely_benign	0.0907	benign	-0.122	Destabilizing	0.025	N	0.693	prob.neutral	None	None	None	None	N
S/M	0.1574	likely_benign	0.1638	benign	-0.386	Destabilizing	0.025	N	0.641	neutral	None	None	None	None	N
S/N	0.2666	likely_benign	0.2747	benign	-1.514	Destabilizing	0.364	N	0.642	neutral	None	None	None	None	N
S/P	0.9706	likely_pathogenic	0.9657	pathogenic	-0.421	Destabilizing	0.822	D	0.72	prob.delet.	N	0.503551597	None	None	N
S/Q	0.5401	ambiguous	0.5553	ambiguous	-1.18	Destabilizing	0.667	D	0.684	prob.neutral	None	None	None	None	N
S/R	0.6105	likely_pathogenic	0.6225	pathogenic	-1.135	Destabilizing	0.667	D	0.725	prob.delet.	None	None	None	None	N
S/T	0.0859	likely_benign	0.0913	benign	-1.129	Destabilizing	0.001	N	0.249	neutral	N	0.446021271	None	None	N
S/V	0.2088	likely_benign	0.22	benign	-0.421	Destabilizing	0.002	N	0.5	neutral	None	None	None	None	N
S/W	0.3479	ambiguous	0.3242	benign	-1.019	Destabilizing	0.883	D	0.729	prob.delet.	None	None	None	None	N
S/Y	0.2104	likely_benign	0.1931	benign	-0.601	Destabilizing	0.272	N	0.719	prob.delet.	N	0.484790303	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.