TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17361	52306;52307;52308	chr2:178609229;178609228;178609227	chr2:179473956;179473955;179473954
N2AB	15720	47383;47384;47385	chr2:178609229;178609228;178609227	chr2:179473956;179473955;179473954
N2A	14793	44602;44603;44604	chr2:178609229;178609228;178609227	chr2:179473956;179473955;179473954
N2B	8296	25111;25112;25113	chr2:178609229;178609228;178609227	chr2:179473956;179473955;179473954
Novex-1	8421	25486;25487;25488	chr2:178609229;178609228;178609227	chr2:179473956;179473955;179473954
Novex-2	8488	25687;25688;25689	chr2:178609229;178609228;178609227	chr2:179473956;179473955;179473954
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-112
• Domain position: 111
• Structural Position: 171
• Q(SASA): 0.5703
• Predicted PPI site: I

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
P/S	None	None	0.001	N	0.201	0.116	0.225215365344	gnomAD-4.0.0	1.86637E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.23532E-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
P/A	0.0668	likely_benign	0.06	benign	-1.155	Destabilizing	0.003	N	0.204	neutral	N	0.439973238	None	None	I
P/C	0.3417	ambiguous	0.3024	benign	-0.693	Destabilizing	0.002	N	0.355	neutral	None	None	None	None	I
P/D	0.3742	ambiguous	0.3394	benign	-0.905	Destabilizing	0.228	N	0.348	neutral	None	None	None	None	I
P/E	0.2372	likely_benign	0.2134	benign	-0.976	Destabilizing	0.228	N	0.353	neutral	None	None	None	None	I
P/F	0.3985	ambiguous	0.3385	benign	-1.148	Destabilizing	0.836	D	0.594	neutral	None	None	None	None	I
P/G	0.2472	likely_benign	0.2206	benign	-1.393	Destabilizing	0.129	N	0.357	neutral	None	None	None	None	I
P/H	0.1756	likely_benign	0.154	benign	-0.999	Destabilizing	0.794	D	0.53	neutral	N	0.456097483	None	None	I
P/I	0.2362	likely_benign	0.2047	benign	-0.632	Destabilizing	0.418	N	0.51	neutral	None	None	None	None	I
P/K	0.2615	likely_benign	0.2355	benign	-0.902	Destabilizing	0.129	N	0.353	neutral	None	None	None	None	I
P/L	0.1209	likely_benign	0.1043	benign	-0.632	Destabilizing	0.101	N	0.387	neutral	N	0.456270842	None	None	I
P/M	0.2566	likely_benign	0.2298	benign	-0.386	Destabilizing	0.94	D	0.534	neutral	None	None	None	None	I
P/N	0.2283	likely_benign	0.2011	benign	-0.545	Destabilizing	0.264	N	0.452	neutral	None	None	None	None	I
P/Q	0.1488	likely_benign	0.1337	benign	-0.801	Destabilizing	0.418	N	0.533	neutral	None	None	None	None	I
P/R	0.1691	likely_benign	0.1527	benign	-0.345	Destabilizing	0.351	N	0.555	neutral	N	0.46277274	None	None	I
P/S	0.0853	likely_benign	0.0772	benign	-0.99	Destabilizing	0.001	N	0.201	neutral	N	0.377441912	None	None	I
P/T	0.0801	likely_benign	0.0723	benign	-0.959	Destabilizing	0.001	N	0.199	neutral	N	0.412709279	None	None	I
P/V	0.159	likely_benign	0.1412	benign	-0.771	Destabilizing	0.129	N	0.381	neutral	None	None	None	None	I
P/W	0.6037	likely_pathogenic	0.5495	ambiguous	-1.262	Destabilizing	0.983	D	0.517	neutral	None	None	None	None	I
P/Y	0.3562	ambiguous	0.3055	benign	-0.978	Destabilizing	0.94	D	0.567	neutral	None	None	None	None	I

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.