TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16635	50128;50129;50130	chr2:178612818;178612817;178612816	chr2:179477545;179477544;179477543
N2AB	14994	45205;45206;45207	chr2:178612818;178612817;178612816	chr2:179477545;179477544;179477543
N2A	14067	42424;42425;42426	chr2:178612818;178612817;178612816	chr2:179477545;179477544;179477543
N2B	7570	22933;22934;22935	chr2:178612818;178612817;178612816	chr2:179477545;179477544;179477543
Novex-1	7695	23308;23309;23310	chr2:178612818;178612817;178612816	chr2:179477545;179477544;179477543
Novex-2	7762	23509;23510;23511	chr2:178612818;178612817;178612816	chr2:179477545;179477544;179477543
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-8
• Domain position: 85
• Structural Position: 119
• Q(SASA): 0.7245
• 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	None	None	0.434	N	0.272	0.15	0.185906805712	gnomAD-4.0.0	1.59427E-06	None	None	None	None	N	None	0	0	None	0	2.79408E-05	None	0	0	0	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	0.2037	likely_benign	0.2565	benign	-0.561	Destabilizing	0.998	D	0.676	prob.neutral	N	0.516640217	None	None	N
E/C	0.9076	likely_pathogenic	0.9366	pathogenic	-0.19	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
E/D	0.1115	likely_benign	0.1071	benign	-0.491	Destabilizing	0.434	N	0.272	neutral	N	0.479012032	None	None	N
E/F	0.8212	likely_pathogenic	0.8653	pathogenic	-0.395	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
E/G	0.2743	likely_benign	0.3767	ambiguous	-0.77	Destabilizing	0.999	D	0.697	prob.neutral	D	0.575703182	None	None	N
E/H	0.6769	likely_pathogenic	0.7615	pathogenic	-0.156	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
E/I	0.4432	ambiguous	0.4998	ambiguous	-0.036	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
E/K	0.2554	likely_benign	0.3665	ambiguous	0.086	Stabilizing	0.998	D	0.631	neutral	N	0.500461895	None	None	N
E/L	0.4302	ambiguous	0.504	ambiguous	-0.036	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
E/M	0.5446	ambiguous	0.6209	pathogenic	0.104	Stabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
E/N	0.3345	likely_benign	0.3927	ambiguous	-0.239	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
E/P	0.4901	ambiguous	0.5373	ambiguous	-0.191	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
E/Q	0.2323	likely_benign	0.293	benign	-0.207	Destabilizing	0.999	D	0.715	prob.delet.	N	0.499503292	None	None	N
E/R	0.4474	ambiguous	0.5779	pathogenic	0.361	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
E/S	0.2592	likely_benign	0.3168	benign	-0.415	Destabilizing	0.997	D	0.655	neutral	None	None	None	None	N
E/T	0.3303	likely_benign	0.3995	ambiguous	-0.247	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
E/V	0.28	likely_benign	0.3415	ambiguous	-0.191	Destabilizing	1.0	D	0.751	deleterious	D	0.574383253	None	None	N
E/W	0.9508	likely_pathogenic	0.969	pathogenic	-0.212	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/Y	0.7368	likely_pathogenic	0.802	pathogenic	-0.154	Destabilizing	1.0	D	0.732	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.