TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7779	23560;23561;23562	chr2:178720427;178720426;178720425	chr2:179585154;179585153;179585152
N2AB	7462	22609;22610;22611	chr2:178720427;178720426;178720425	chr2:179585154;179585153;179585152
N2A	6535	19828;19829;19830	chr2:178720427;178720426;178720425	chr2:179585154;179585153;179585152
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-62
• Domain position: 78
• Structural Position: 162
• Q(SASA): 0.9802
• 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
E/D	rs1253898130	None	0.014	N	0.341	0.226	0.200317383148	gnomAD-4.0.0	3.18402E-06	None	None	None	None	I	None	0	0	None	0	5.54662E-05	None	0	0	0	0	0
E/K	rs1314203498	None	0.822	N	0.474	0.342	0.40528724903	gnomAD-4.0.0	6.84315E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99572E-07	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	0.27	likely_benign	0.2411	benign	-0.027	Destabilizing	0.489	N	0.481	neutral	N	0.484286949	None	None	I
E/C	0.9596	likely_pathogenic	0.9575	pathogenic	-0.258	Destabilizing	0.998	D	0.628	neutral	None	None	None	None	I
E/D	0.1134	likely_benign	0.1122	benign	-0.453	Destabilizing	0.014	N	0.341	neutral	N	0.484807024	None	None	I
E/F	0.9186	likely_pathogenic	0.9116	pathogenic	-0.12	Destabilizing	0.993	D	0.573	neutral	None	None	None	None	I
E/G	0.3731	ambiguous	0.3407	ambiguous	-0.118	Destabilizing	0.014	N	0.336	neutral	N	0.503123426	None	None	I
E/H	0.756	likely_pathogenic	0.7408	pathogenic	0.527	Stabilizing	0.998	D	0.462	neutral	None	None	None	None	I
E/I	0.562	ambiguous	0.5325	ambiguous	0.151	Stabilizing	0.978	D	0.567	neutral	None	None	None	None	I
E/K	0.3911	ambiguous	0.3693	ambiguous	0.343	Stabilizing	0.822	D	0.474	neutral	N	0.506854378	None	None	I
E/L	0.68	likely_pathogenic	0.6522	pathogenic	0.151	Stabilizing	0.978	D	0.525	neutral	None	None	None	None	I
E/M	0.7131	likely_pathogenic	0.678	pathogenic	-0.078	Destabilizing	0.998	D	0.563	neutral	None	None	None	None	I
E/N	0.4535	ambiguous	0.4276	ambiguous	0.117	Stabilizing	0.86	D	0.443	neutral	None	None	None	None	I
E/P	0.7827	likely_pathogenic	0.7531	pathogenic	0.108	Stabilizing	0.978	D	0.497	neutral	None	None	None	None	I
E/Q	0.3259	likely_benign	0.3132	benign	0.111	Stabilizing	0.97	D	0.447	neutral	N	0.499179044	None	None	I
E/R	0.5719	likely_pathogenic	0.5536	ambiguous	0.563	Stabilizing	0.978	D	0.45	neutral	None	None	None	None	I
E/S	0.354	ambiguous	0.3258	benign	-0.006	Destabilizing	0.193	N	0.352	neutral	None	None	None	None	I
E/T	0.4187	ambiguous	0.3944	ambiguous	0.077	Stabilizing	0.754	D	0.487	neutral	None	None	None	None	I
E/V	0.3693	ambiguous	0.341	ambiguous	0.108	Stabilizing	0.97	D	0.498	neutral	N	0.501757989	None	None	I
E/W	0.9746	likely_pathogenic	0.9735	pathogenic	-0.096	Destabilizing	0.998	D	0.654	neutral	None	None	None	None	I
E/Y	0.8573	likely_pathogenic	0.8508	pathogenic	0.093	Stabilizing	0.993	D	0.549	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.