TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3394	10405;10406;10407	chr2:178759107;178759106;178759105	chr2:179623834;179623833;179623832
N2AB	3394	10405;10406;10407	chr2:178759107;178759106;178759105	chr2:179623834;179623833;179623832
N2A	3394	10405;10406;10407	chr2:178759107;178759106;178759105	chr2:179623834;179623833;179623832
N2B	3348	10267;10268;10269	chr2:178759107;178759106;178759105	chr2:179623834;179623833;179623832
Novex-1	3348	10267;10268;10269	chr2:178759107;178759106;178759105	chr2:179623834;179623833;179623832
Novex-2	3348	10267;10268;10269	chr2:178759107;178759106;178759105	chr2:179623834;179623833;179623832
Novex-3	3394	10405;10406;10407	chr2:178759107;178759106;178759105	chr2:179623834;179623833;179623832

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Ig-24
• Domain position: 50
• Structural Position: 127
• Q(SASA): 0.2666
• 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
Q/R	None	None	0.99	N	0.641	0.467	0.281780670237	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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
Q/A	0.2631	likely_benign	0.2881	benign	-0.6	Destabilizing	0.993	D	0.61	neutral	None	None	None	None	I
Q/C	0.7699	likely_pathogenic	0.7676	pathogenic	0.006	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
Q/D	0.6074	likely_pathogenic	0.6466	pathogenic	0.149	Stabilizing	0.971	D	0.611	neutral	None	None	None	None	I
Q/E	0.1171	likely_benign	0.1296	benign	0.199	Stabilizing	0.953	D	0.525	neutral	N	0.498591116	None	None	I
Q/F	0.8286	likely_pathogenic	0.848	pathogenic	-0.551	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	I
Q/G	0.4646	ambiguous	0.4931	ambiguous	-0.877	Destabilizing	0.985	D	0.659	neutral	None	None	None	None	I
Q/H	0.3085	likely_benign	0.3276	benign	-0.63	Destabilizing	0.997	D	0.62	neutral	N	0.511373087	None	None	I
Q/I	0.5458	ambiguous	0.5677	pathogenic	0.073	Stabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	I
Q/K	0.1446	likely_benign	0.1701	benign	-0.061	Destabilizing	0.98	D	0.602	neutral	N	0.505489797	None	None	I
Q/L	0.2527	likely_benign	0.268	benign	0.073	Stabilizing	0.99	D	0.642	neutral	N	0.509622063	None	None	I
Q/M	0.5373	ambiguous	0.5323	ambiguous	0.335	Stabilizing	0.999	D	0.617	neutral	None	None	None	None	I
Q/N	0.432	ambiguous	0.4519	ambiguous	-0.578	Destabilizing	0.469	N	0.333	neutral	None	None	None	None	I
Q/P	0.2917	likely_benign	0.374	ambiguous	-0.121	Destabilizing	0.999	D	0.628	neutral	N	0.500899893	None	None	I
Q/R	0.1292	likely_benign	0.147	benign	0.021	Stabilizing	0.99	D	0.641	neutral	N	0.510152989	None	None	I
Q/S	0.3046	likely_benign	0.3383	benign	-0.659	Destabilizing	0.985	D	0.59	neutral	None	None	None	None	I
Q/T	0.2809	likely_benign	0.303	benign	-0.416	Destabilizing	0.985	D	0.625	neutral	None	None	None	None	I
Q/V	0.3623	ambiguous	0.3795	ambiguous	-0.121	Destabilizing	0.999	D	0.643	neutral	None	None	None	None	I
Q/W	0.7425	likely_pathogenic	0.7567	pathogenic	-0.437	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	I
Q/Y	0.613	likely_pathogenic	0.6536	pathogenic	-0.215	Destabilizing	0.999	D	0.611	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.