TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20029	60310;60311;60312	chr2:178591734;178591733;178591732	chr2:179456461;179456460;179456459
N2AB	18388	55387;55388;55389	chr2:178591734;178591733;178591732	chr2:179456461;179456460;179456459
N2A	17461	52606;52607;52608	chr2:178591734;178591733;178591732	chr2:179456461;179456460;179456459
N2B	10964	33115;33116;33117	chr2:178591734;178591733;178591732	chr2:179456461;179456460;179456459
Novex-1	11089	33490;33491;33492	chr2:178591734;178591733;178591732	chr2:179456461;179456460;179456459
Novex-2	11156	33691;33692;33693	chr2:178591734;178591733;178591732	chr2:179456461;179456460;179456459
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-33
• Domain position: 53
• Structural Position: 72
• Q(SASA): 0.5088
• 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/I	None	None	0.884	N	0.343	0.354	0.316198179892	gnomAD-4.0.0	6.84351E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99604E-07	0	0
T/N	rs2050252504	None	1.0	N	0.67	0.35	0.319686207203	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
T/N	rs2050252504	None	1.0	N	0.67	0.35	0.319686207203	gnomAD-4.0.0	2.47957E-06	None	None	None	None	N	None	2.67251E-05	0	None	0	0	None	0	0	1.69556E-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
T/A	0.1058	likely_benign	0.1123	benign	-0.389	Destabilizing	0.998	D	0.442	neutral	N	0.503933424	None	None	N
T/C	0.5179	ambiguous	0.5764	pathogenic	-0.364	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
T/D	0.4562	ambiguous	0.4658	ambiguous	0.399	Stabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
T/E	0.302	likely_benign	0.3111	benign	0.349	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
T/F	0.3508	ambiguous	0.3677	ambiguous	-0.718	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
T/G	0.408	ambiguous	0.4267	ambiguous	-0.559	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
T/H	0.27	likely_benign	0.2812	benign	-0.813	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
T/I	0.1485	likely_benign	0.1625	benign	-0.055	Destabilizing	0.884	D	0.343	neutral	N	0.464870643	None	None	N
T/K	0.1644	likely_benign	0.1699	benign	-0.371	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
T/L	0.1103	likely_benign	0.1205	benign	-0.055	Destabilizing	0.994	D	0.521	neutral	None	None	None	None	N
T/M	0.085	likely_benign	0.0857	benign	0.001	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
T/N	0.1345	likely_benign	0.1401	benign	-0.222	Destabilizing	1.0	D	0.67	neutral	N	0.486387813	None	None	N
T/P	0.1765	likely_benign	0.2011	benign	-0.135	Destabilizing	1.0	D	0.756	deleterious	N	0.460222719	None	None	N
T/Q	0.2387	likely_benign	0.2446	benign	-0.401	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
T/R	0.1564	likely_benign	0.1667	benign	-0.148	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
T/S	0.1753	likely_benign	0.1808	benign	-0.491	Destabilizing	0.999	D	0.463	neutral	N	0.504512214	None	None	N
T/V	0.1218	likely_benign	0.1338	benign	-0.135	Destabilizing	0.985	D	0.453	neutral	None	None	None	None	N
T/W	0.6409	likely_pathogenic	0.6588	pathogenic	-0.698	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
T/Y	0.3	likely_benign	0.3295	benign	-0.424	Destabilizing	1.0	D	0.791	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.