TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14366	43321;43322;43323	chr2:178633035;178633034;178633033	chr2:179497762;179497761;179497760
N2AB	12725	38398;38399;38400	chr2:178633035;178633034;178633033	chr2:179497762;179497761;179497760
N2A	11798	35617;35618;35619	chr2:178633035;178633034;178633033	chr2:179497762;179497761;179497760
N2B	5301	16126;16127;16128	chr2:178633035;178633034;178633033	chr2:179497762;179497761;179497760
Novex-1	5426	16501;16502;16503	chr2:178633035;178633034;178633033	chr2:179497762;179497761;179497760
Novex-2	5493	16702;16703;16704	chr2:178633035;178633034;178633033	chr2:179497762;179497761;179497760
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-94
• Domain position: 48
• Structural Position: 123
• Q(SASA): 0.1125
• 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
I/V	None	None	0.264	N	0.336	0.164	0.426084969639	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
I/A	0.8748	likely_pathogenic	0.8493	pathogenic	-2.204	Highly Destabilizing	0.841	D	0.596	neutral	None	None	None	None	N
I/C	0.9439	likely_pathogenic	0.9423	pathogenic	-1.213	Destabilizing	0.998	D	0.661	prob.neutral	None	None	None	None	N
I/D	0.9682	likely_pathogenic	0.964	pathogenic	-2.155	Highly Destabilizing	0.991	D	0.797	deleterious	None	None	None	None	N
I/E	0.9007	likely_pathogenic	0.8833	pathogenic	-2.05	Highly Destabilizing	0.974	D	0.803	deleterious	None	None	None	None	N
I/F	0.3192	likely_benign	0.2911	benign	-1.412	Destabilizing	0.933	D	0.521	neutral	N	0.474267842	None	None	N
I/G	0.9623	likely_pathogenic	0.9556	pathogenic	-2.635	Highly Destabilizing	0.974	D	0.792	deleterious	None	None	None	None	N
I/H	0.8933	likely_pathogenic	0.8883	pathogenic	-1.98	Destabilizing	0.998	D	0.767	deleterious	None	None	None	None	N
I/K	0.7677	likely_pathogenic	0.7725	pathogenic	-1.708	Destabilizing	0.949	D	0.791	deleterious	None	None	None	None	N
I/L	0.2653	likely_benign	0.2408	benign	-1.019	Destabilizing	0.11	N	0.205	neutral	N	0.416855006	None	None	N
I/M	0.1264	likely_benign	0.1275	benign	-0.71	Destabilizing	0.134	N	0.258	neutral	N	0.437972818	None	None	N
I/N	0.7051	likely_pathogenic	0.7108	pathogenic	-1.66	Destabilizing	0.966	D	0.805	deleterious	D	0.614264342	None	None	N
I/P	0.9805	likely_pathogenic	0.9763	pathogenic	-1.389	Destabilizing	0.991	D	0.797	deleterious	None	None	None	None	N
I/Q	0.8379	likely_pathogenic	0.8292	pathogenic	-1.719	Destabilizing	0.974	D	0.807	deleterious	None	None	None	None	N
I/R	0.7217	likely_pathogenic	0.7261	pathogenic	-1.19	Destabilizing	0.974	D	0.798	deleterious	None	None	None	None	N
I/S	0.8185	likely_pathogenic	0.8092	pathogenic	-2.269	Highly Destabilizing	0.966	D	0.726	deleterious	N	0.50289534	None	None	N
I/T	0.7221	likely_pathogenic	0.6984	pathogenic	-2.044	Highly Destabilizing	0.799	D	0.663	prob.neutral	D	0.571317044	None	None	N
I/V	0.1912	likely_benign	0.1718	benign	-1.389	Destabilizing	0.264	N	0.336	neutral	N	0.452019276	None	None	N
I/W	0.9115	likely_pathogenic	0.9058	pathogenic	-1.68	Destabilizing	0.998	D	0.761	deleterious	None	None	None	None	N
I/Y	0.7166	likely_pathogenic	0.7204	pathogenic	-1.431	Destabilizing	0.974	D	0.647	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.