TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19272	58039;58040;58041	chr2:178595540;178595539;178595538	chr2:179460267;179460266;179460265
N2AB	17631	53116;53117;53118	chr2:178595540;178595539;178595538	chr2:179460267;179460266;179460265
N2A	16704	50335;50336;50337	chr2:178595540;178595539;178595538	chr2:179460267;179460266;179460265
N2B	10207	30844;30845;30846	chr2:178595540;178595539;178595538	chr2:179460267;179460266;179460265
Novex-1	10332	31219;31220;31221	chr2:178595540;178595539;178595538	chr2:179460267;179460266;179460265
Novex-2	10399	31420;31421;31422	chr2:178595540;178595539;178595538	chr2:179460267;179460266;179460265
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: Fn3-27
• Domain position: 90
• Structural Position: 123
• Q(SASA): 0.1173
• 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	0.997	N	0.703	0.269	0.204665344411	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
T/I	rs1049715521	None	0.999	N	0.886	0.355	0.423119698836	gnomAD-4.0.0	5.66484E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.45084E-06	1.24772E-05	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	0.2537	likely_benign	0.285	benign	-0.806	Destabilizing	0.997	D	0.703	prob.delet.	N	0.495849871	None	None	N
T/C	0.7104	likely_pathogenic	0.6941	pathogenic	-0.239	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
T/D	0.8071	likely_pathogenic	0.8581	pathogenic	0.299	Stabilizing	0.999	D	0.879	deleterious	None	None	None	None	N
T/E	0.8173	likely_pathogenic	0.8693	pathogenic	0.433	Stabilizing	0.999	D	0.877	deleterious	None	None	None	None	N
T/F	0.6862	likely_pathogenic	0.7098	pathogenic	-0.69	Destabilizing	0.999	D	0.877	deleterious	None	None	None	None	N
T/G	0.5394	ambiguous	0.5491	ambiguous	-1.154	Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	N
T/H	0.7659	likely_pathogenic	0.8082	pathogenic	-1.124	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
T/I	0.4695	ambiguous	0.5092	ambiguous	0.076	Stabilizing	0.999	D	0.886	deleterious	N	0.513454197	None	None	N
T/K	0.783	likely_pathogenic	0.8408	pathogenic	0.225	Stabilizing	0.999	D	0.881	deleterious	N	0.470351145	None	None	N
T/L	0.2244	likely_benign	0.2165	benign	0.076	Stabilizing	0.998	D	0.785	deleterious	None	None	None	None	N
T/M	0.1557	likely_benign	0.1593	benign	-0.047	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
T/N	0.3657	ambiguous	0.412	ambiguous	-0.131	Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
T/P	0.6845	likely_pathogenic	0.7615	pathogenic	-0.187	Destabilizing	0.999	D	0.85	deleterious	N	0.473549015	None	None	N
T/Q	0.7216	likely_pathogenic	0.7734	pathogenic	-0.024	Destabilizing	0.999	D	0.838	deleterious	None	None	None	None	N
T/R	0.7716	likely_pathogenic	0.835	pathogenic	0.086	Stabilizing	0.999	D	0.849	deleterious	N	0.4780866	None	None	N
T/S	0.2507	likely_benign	0.2629	benign	-0.563	Destabilizing	0.997	D	0.694	prob.delet.	N	0.490001334	None	None	N
T/V	0.3944	ambiguous	0.4224	ambiguous	-0.187	Destabilizing	0.998	D	0.713	prob.delet.	None	None	None	None	N
T/W	0.934	likely_pathogenic	0.9424	pathogenic	-0.676	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
T/Y	0.7794	likely_pathogenic	0.8187	pathogenic	-0.311	Destabilizing	1.0	D	0.892	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.