TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19271	58036;58037;58038	chr2:178595543;178595542;178595541	chr2:179460270;179460269;179460268
N2AB	17630	53113;53114;53115	chr2:178595543;178595542;178595541	chr2:179460270;179460269;179460268
N2A	16703	50332;50333;50334	chr2:178595543;178595542;178595541	chr2:179460270;179460269;179460268
N2B	10206	30841;30842;30843	chr2:178595543;178595542;178595541	chr2:179460270;179460269;179460268
Novex-1	10331	31216;31217;31218	chr2:178595543;178595542;178595541	chr2:179460270;179460269;179460268
Novex-2	10398	31417;31418;31419	chr2:178595543;178595542;178595541	chr2:179460270;179460269;179460268
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-27
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.2129
• 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
E/K	rs2051339525	None	0.997	N	0.849	0.428	0.432266382184	gnomAD-4.0.0	1.72222E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.08629E-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
E/A	0.2734	likely_benign	0.3607	ambiguous	-0.141	Destabilizing	0.997	D	0.774	deleterious	N	0.467619348	None	None	N
E/C	0.9177	likely_pathogenic	0.945	pathogenic	-0.024	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/D	0.4046	ambiguous	0.4338	ambiguous	-0.894	Destabilizing	0.997	D	0.801	deleterious	N	0.464363664	None	None	N
E/F	0.93	likely_pathogenic	0.9549	pathogenic	0.774	Stabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
E/G	0.4942	ambiguous	0.6088	pathogenic	-0.572	Destabilizing	0.999	D	0.695	prob.delet.	N	0.476595797	None	None	N
E/H	0.7992	likely_pathogenic	0.8617	pathogenic	0.66	Stabilizing	1.0	D	0.699	prob.delet.	None	None	None	None	N
E/I	0.6331	likely_pathogenic	0.7244	pathogenic	1.05	Stabilizing	0.999	D	0.842	deleterious	None	None	None	None	N
E/K	0.4422	ambiguous	0.5956	pathogenic	-0.065	Destabilizing	0.997	D	0.849	deleterious	N	0.4703416	None	None	N
E/L	0.6905	likely_pathogenic	0.7745	pathogenic	1.05	Stabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
E/M	0.6557	likely_pathogenic	0.7407	pathogenic	1.327	Stabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
E/N	0.642	likely_pathogenic	0.7116	pathogenic	-0.81	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
E/P	0.7174	likely_pathogenic	0.8154	pathogenic	0.676	Stabilizing	0.999	D	0.693	prob.delet.	None	None	None	None	N
E/Q	0.244	likely_benign	0.3115	benign	-0.578	Destabilizing	0.999	D	0.757	deleterious	N	0.502663987	None	None	N
E/R	0.6373	likely_pathogenic	0.7499	pathogenic	0.24	Stabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
E/S	0.4161	ambiguous	0.5117	ambiguous	-1.147	Destabilizing	0.998	D	0.801	deleterious	None	None	None	None	N
E/T	0.4263	ambiguous	0.5068	ambiguous	-0.765	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
E/V	0.3958	ambiguous	0.4771	ambiguous	0.676	Stabilizing	0.999	D	0.758	deleterious	N	0.476800061	None	None	N
E/W	0.9814	likely_pathogenic	0.9891	pathogenic	1.001	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/Y	0.9012	likely_pathogenic	0.936	pathogenic	1.077	Stabilizing	1.0	D	0.851	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.