TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7554	22885;22886;22887	chr2:178722003;178722002;178722001	chr2:179586730;179586729;179586728
N2AB	7237	21934;21935;21936	chr2:178722003;178722002;178722001	chr2:179586730;179586729;179586728
N2A	6310	19153;19154;19155	chr2:178722003;178722002;178722001	chr2:179586730;179586729;179586728
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-60
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.4288
• 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/D	rs879075975	None	0.003	D	0.18	0.115	0.371344866733	gnomAD-4.0.0	1.36866E-06	None	None	None	None	N	None	2.98918E-05	0	None	0	0	None	0	0	8.99619E-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	0.2316	likely_benign	0.2378	benign	-0.383	Destabilizing	0.975	D	0.576	neutral	N	0.480187851	None	None	N
E/C	0.9614	likely_pathogenic	0.9631	pathogenic	-0.019	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
E/D	0.1489	likely_benign	0.1407	benign	-0.393	Destabilizing	0.003	N	0.18	neutral	D	0.527266935	None	None	N
E/F	0.902	likely_pathogenic	0.9022	pathogenic	-0.246	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
E/G	0.3968	ambiguous	0.4041	ambiguous	-0.591	Destabilizing	0.985	D	0.591	neutral	N	0.495002081	None	None	N
E/H	0.7965	likely_pathogenic	0.8113	pathogenic	-0.082	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	N
E/I	0.4469	ambiguous	0.4314	ambiguous	0.132	Stabilizing	0.998	D	0.773	deleterious	None	None	None	None	N
E/K	0.4376	ambiguous	0.448	ambiguous	0.344	Stabilizing	0.973	D	0.518	neutral	N	0.496925386	None	None	N
E/L	0.5393	ambiguous	0.5472	ambiguous	0.132	Stabilizing	0.994	D	0.771	deleterious	None	None	None	None	N
E/M	0.6101	likely_pathogenic	0.605	pathogenic	0.233	Stabilizing	0.997	D	0.708	prob.delet.	None	None	None	None	N
E/N	0.4374	ambiguous	0.447	ambiguous	-0.01	Destabilizing	0.974	D	0.592	neutral	None	None	None	None	N
E/P	0.4811	ambiguous	0.494	ambiguous	-0.019	Destabilizing	0.986	D	0.722	prob.delet.	None	None	None	None	N
E/Q	0.2938	likely_benign	0.3079	benign	0.032	Stabilizing	0.995	D	0.573	neutral	N	0.502909995	None	None	N
E/R	0.6224	likely_pathogenic	0.6508	pathogenic	0.515	Stabilizing	0.997	D	0.662	neutral	None	None	None	None	N
E/S	0.4489	ambiguous	0.4706	ambiguous	-0.155	Destabilizing	0.963	D	0.522	neutral	None	None	None	None	N
E/T	0.3938	ambiguous	0.3851	ambiguous	0.016	Stabilizing	0.996	D	0.649	neutral	None	None	None	None	N
E/V	0.2631	likely_benign	0.2451	benign	-0.019	Destabilizing	0.996	D	0.737	prob.delet.	N	0.498658969	None	None	N
E/W	0.973	likely_pathogenic	0.976	pathogenic	-0.089	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
E/Y	0.8326	likely_pathogenic	0.8335	pathogenic	0.002	Stabilizing	1.0	D	0.72	prob.delet.	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.