TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21695	65308;65309;65310	chr2:178584468;178584467;178584466	chr2:179449195;179449194;179449193
N2AB	20054	60385;60386;60387	chr2:178584468;178584467;178584466	chr2:179449195;179449194;179449193
N2A	19127	57604;57605;57606	chr2:178584468;178584467;178584466	chr2:179449195;179449194;179449193
N2B	12630	38113;38114;38115	chr2:178584468;178584467;178584466	chr2:179449195;179449194;179449193
Novex-1	12755	38488;38489;38490	chr2:178584468;178584467;178584466	chr2:179449195;179449194;179449193
Novex-2	12822	38689;38690;38691	chr2:178584468;178584467;178584466	chr2:179449195;179449194;179449193
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Fn3-45
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.1958
• 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
L/R	rs1174402887	-1.559	0.989	N	0.632	0.3	0.729612430995	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
L/R	rs1174402887	-1.559	0.989	N	0.632	0.3	0.729612430995	gnomAD-4.0.0	1.59233E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43299E-05	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
L/A	0.2543	likely_benign	0.2271	benign	-2.297	Highly Destabilizing	0.525	D	0.593	neutral	None	None	None	None	N
L/C	0.3745	ambiguous	0.3601	ambiguous	-1.351	Destabilizing	0.016	N	0.493	neutral	None	None	None	None	N
L/D	0.7641	likely_pathogenic	0.7455	pathogenic	-2.512	Highly Destabilizing	0.991	D	0.652	neutral	None	None	None	None	N
L/E	0.4061	ambiguous	0.3815	ambiguous	-2.291	Highly Destabilizing	0.974	D	0.66	neutral	None	None	None	None	N
L/F	0.1082	likely_benign	0.1005	benign	-1.308	Destabilizing	0.037	N	0.48	neutral	None	None	None	None	N
L/G	0.6195	likely_pathogenic	0.5959	pathogenic	-2.817	Highly Destabilizing	0.974	D	0.659	neutral	None	None	None	None	N
L/H	0.136	likely_benign	0.1365	benign	-2.313	Highly Destabilizing	0.998	D	0.673	neutral	None	None	None	None	N
L/I	0.0823	likely_benign	0.0765	benign	-0.798	Destabilizing	0.067	N	0.479	neutral	None	None	None	None	N
L/K	0.2791	likely_benign	0.286	benign	-1.685	Destabilizing	0.974	D	0.631	neutral	None	None	None	None	N
L/M	0.0917	likely_benign	0.09	benign	-0.69	Destabilizing	0.966	D	0.661	neutral	N	0.463628384	None	None	N
L/N	0.3462	ambiguous	0.3262	benign	-1.991	Destabilizing	0.991	D	0.671	neutral	None	None	None	None	N
L/P	0.969	likely_pathogenic	0.9694	pathogenic	-1.279	Destabilizing	0.989	D	0.673	neutral	D	0.522713973	None	None	N
L/Q	0.1238	likely_benign	0.12	benign	-1.852	Destabilizing	0.989	D	0.623	neutral	N	0.456507623	None	None	N
L/R	0.187	likely_benign	0.187	benign	-1.432	Destabilizing	0.989	D	0.632	neutral	N	0.43536156	None	None	N
L/S	0.2843	likely_benign	0.2564	benign	-2.647	Highly Destabilizing	0.915	D	0.625	neutral	None	None	None	None	N
L/T	0.1894	likely_benign	0.1672	benign	-2.294	Highly Destabilizing	0.842	D	0.616	neutral	None	None	None	None	N
L/V	0.0786	likely_benign	0.073	benign	-1.279	Destabilizing	0.012	N	0.391	neutral	N	0.406292234	None	None	N
L/W	0.2427	likely_benign	0.2526	benign	-1.732	Destabilizing	0.998	D	0.64	neutral	None	None	None	None	N
L/Y	0.2327	likely_benign	0.2377	benign	-1.414	Destabilizing	0.904	D	0.651	neutral	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.