TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17682	53269;53270;53271	chr2:178607644;178607643;178607642	chr2:179472371;179472370;179472369
N2AB	16041	48346;48347;48348	chr2:178607644;178607643;178607642	chr2:179472371;179472370;179472369
N2A	15114	45565;45566;45567	chr2:178607644;178607643;178607642	chr2:179472371;179472370;179472369
N2B	8617	26074;26075;26076	chr2:178607644;178607643;178607642	chr2:179472371;179472370;179472369
Novex-1	8742	26449;26450;26451	chr2:178607644;178607643;178607642	chr2:179472371;179472370;179472369
Novex-2	8809	26650;26651;26652	chr2:178607644;178607643;178607642	chr2:179472371;179472370;179472369
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-113
• Domain position: 6
• Structural Position: 13
• Q(SASA): 0.2727
• 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
I/T	None	None	0.051	N	0.26	0.311	0.655104906463	gnomAD-4.0.0	2.40065E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.62501E-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	0.8769	likely_pathogenic	0.8684	pathogenic	-2.035	Highly Destabilizing	0.525	D	0.388	neutral	None	None	None	None	I
I/C	0.8581	likely_pathogenic	0.8431	pathogenic	-1.48	Destabilizing	0.998	D	0.473	neutral	None	None	None	None	I
I/D	0.9784	likely_pathogenic	0.9829	pathogenic	-1.54	Destabilizing	0.974	D	0.548	neutral	None	None	None	None	I
I/E	0.922	likely_pathogenic	0.9379	pathogenic	-1.437	Destabilizing	0.974	D	0.551	neutral	None	None	None	None	I
I/F	0.2715	likely_benign	0.2824	benign	-1.235	Destabilizing	0.949	D	0.485	neutral	None	None	None	None	I
I/G	0.9628	likely_pathogenic	0.9659	pathogenic	-2.468	Highly Destabilizing	0.915	D	0.543	neutral	None	None	None	None	I
I/H	0.8539	likely_pathogenic	0.8736	pathogenic	-1.724	Destabilizing	0.998	D	0.559	neutral	None	None	None	None	I
I/K	0.7758	likely_pathogenic	0.8172	pathogenic	-1.542	Destabilizing	0.966	D	0.553	neutral	N	0.517783447	None	None	I
I/L	0.1645	likely_benign	0.1575	benign	-0.862	Destabilizing	0.267	N	0.328	neutral	N	0.421888909	None	None	I
I/M	0.192	likely_benign	0.1813	benign	-0.834	Destabilizing	0.966	D	0.503	neutral	N	0.491039563	None	None	I
I/N	0.8049	likely_pathogenic	0.832	pathogenic	-1.54	Destabilizing	0.974	D	0.571	neutral	None	None	None	None	I
I/P	0.978	likely_pathogenic	0.9826	pathogenic	-1.225	Destabilizing	0.991	D	0.565	neutral	None	None	None	None	I
I/Q	0.8026	likely_pathogenic	0.831	pathogenic	-1.569	Destabilizing	0.991	D	0.59	neutral	None	None	None	None	I
I/R	0.7579	likely_pathogenic	0.8022	pathogenic	-1.096	Destabilizing	0.966	D	0.581	neutral	N	0.486190217	None	None	I
I/S	0.8555	likely_pathogenic	0.8593	pathogenic	-2.25	Highly Destabilizing	0.728	D	0.482	neutral	None	None	None	None	I
I/T	0.7886	likely_pathogenic	0.7837	pathogenic	-2.01	Highly Destabilizing	0.051	N	0.26	neutral	N	0.485748387	None	None	I
I/V	0.1468	likely_benign	0.1296	benign	-1.225	Destabilizing	0.002	N	0.131	neutral	N	0.429273455	None	None	I
I/W	0.8844	likely_pathogenic	0.8989	pathogenic	-1.397	Destabilizing	0.998	D	0.601	neutral	None	None	None	None	I
I/Y	0.716	likely_pathogenic	0.7409	pathogenic	-1.151	Destabilizing	0.974	D	0.508	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.