TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15138	45637;45638;45639	chr2:178621306;178621305;178621304	chr2:179486033;179486032;179486031
N2AB	13497	40714;40715;40716	chr2:178621306;178621305;178621304	chr2:179486033;179486032;179486031
N2A	12570	37933;37934;37935	chr2:178621306;178621305;178621304	chr2:179486033;179486032;179486031
N2B	6073	18442;18443;18444	chr2:178621306;178621305;178621304	chr2:179486033;179486032;179486031
Novex-1	6198	18817;18818;18819	chr2:178621306;178621305;178621304	chr2:179486033;179486032;179486031
Novex-2	6265	19018;19019;19020	chr2:178621306;178621305;178621304	chr2:179486033;179486032;179486031
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: Ig-103
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.3144
• 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/V	None	None	0.263	N	0.474	0.178	0.310147130316	gnomAD-4.0.0	1.59503E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43484E-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
E/A	0.2738	likely_benign	0.2565	benign	-0.301	Destabilizing	0.826	D	0.5	neutral	N	0.439096062	None	None	N
E/C	0.9601	likely_pathogenic	0.9472	pathogenic	-0.309	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	N
E/D	0.3961	ambiguous	0.3957	ambiguous	-0.833	Destabilizing	0.035	N	0.407	neutral	N	0.470074969	None	None	N
E/F	0.9271	likely_pathogenic	0.9138	pathogenic	0.489	Stabilizing	0.991	D	0.621	neutral	None	None	None	None	N
E/G	0.4903	ambiguous	0.4654	ambiguous	-0.661	Destabilizing	0.959	D	0.544	neutral	D	0.529014982	None	None	N
E/H	0.737	likely_pathogenic	0.6874	pathogenic	0.537	Stabilizing	0.991	D	0.566	neutral	None	None	None	None	N
E/I	0.5307	ambiguous	0.4907	ambiguous	0.669	Stabilizing	0.964	D	0.611	neutral	None	None	None	None	N
E/K	0.3075	likely_benign	0.2692	benign	-0.02	Destabilizing	0.852	D	0.583	neutral	N	0.449147714	None	None	N
E/L	0.6881	likely_pathogenic	0.6566	pathogenic	0.669	Stabilizing	0.884	D	0.533	neutral	None	None	None	None	N
E/M	0.6612	likely_pathogenic	0.6211	pathogenic	0.723	Stabilizing	0.998	D	0.599	neutral	None	None	None	None	N
E/N	0.4981	ambiguous	0.4869	ambiguous	-0.766	Destabilizing	0.939	D	0.551	neutral	None	None	None	None	N
E/P	0.9712	likely_pathogenic	0.97	pathogenic	0.368	Stabilizing	0.997	D	0.589	neutral	None	None	None	None	N
E/Q	0.2032	likely_benign	0.183	benign	-0.584	Destabilizing	0.509	D	0.442	neutral	N	0.450957108	None	None	N
E/R	0.5276	ambiguous	0.4546	ambiguous	0.363	Stabilizing	0.982	D	0.58	neutral	None	None	None	None	N
E/S	0.3284	likely_benign	0.3022	benign	-0.973	Destabilizing	0.884	D	0.551	neutral	None	None	None	None	N
E/T	0.2909	likely_benign	0.2777	benign	-0.655	Destabilizing	0.17	N	0.415	neutral	None	None	None	None	N
E/V	0.2993	likely_benign	0.2778	benign	0.368	Stabilizing	0.263	N	0.474	neutral	N	0.429728552	None	None	N
E/W	0.9851	likely_pathogenic	0.9804	pathogenic	0.761	Stabilizing	0.999	D	0.647	neutral	None	None	None	None	N
E/Y	0.8878	likely_pathogenic	0.8667	pathogenic	0.775	Stabilizing	0.997	D	0.605	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.