TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5748	17467;17468;17469	chr2:178731524;178731523;178731522	chr2:179596251;179596250;179596249
N2AB	5431	16516;16517;16518	chr2:178731524;178731523;178731522	chr2:179596251;179596250;179596249
N2A	4504	13735;13736;13737	chr2:178731524;178731523;178731522	chr2:179596251;179596250;179596249
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: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-41
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.2606
• 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
A/D	rs772161489	-0.489	0.801	N	0.517	0.167	0.413503789086	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
A/D	rs772161489	-0.489	0.801	N	0.517	0.167	0.413503789086	gnomAD-4.0.0	3.18514E-06	None	None	None	None	N	None	0	2.28959E-05	None	0	0	None	0	0	2.86022E-06	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
A/C	0.5011	ambiguous	0.4554	ambiguous	-0.546	Destabilizing	0.998	D	0.507	neutral	None	None	None	None	N
A/D	0.4439	ambiguous	0.3684	ambiguous	-0.513	Destabilizing	0.801	D	0.517	neutral	N	0.461422293	None	None	N
A/E	0.3496	ambiguous	0.2713	benign	-0.475	Destabilizing	0.842	D	0.474	neutral	None	None	None	None	N
A/F	0.327	likely_benign	0.2969	benign	-0.47	Destabilizing	0.949	D	0.57	neutral	None	None	None	None	N
A/G	0.2085	likely_benign	0.1968	benign	-0.794	Destabilizing	0.625	D	0.503	neutral	N	0.461595651	None	None	N
A/H	0.4843	ambiguous	0.426	ambiguous	-0.864	Destabilizing	0.998	D	0.563	neutral	None	None	None	None	N
A/I	0.2118	likely_benign	0.1888	benign	0.207	Stabilizing	0.728	D	0.471	neutral	None	None	None	None	N
A/K	0.5264	ambiguous	0.4303	ambiguous	-0.688	Destabilizing	0.067	N	0.366	neutral	None	None	None	None	N
A/L	0.1907	likely_benign	0.1748	benign	0.207	Stabilizing	0.525	D	0.494	neutral	None	None	None	None	N
A/M	0.23	likely_benign	0.2114	benign	-0.01	Destabilizing	0.974	D	0.527	neutral	None	None	None	None	N
A/N	0.2829	likely_benign	0.2565	benign	-0.597	Destabilizing	0.842	D	0.542	neutral	None	None	None	None	N
A/P	0.6441	likely_pathogenic	0.6361	pathogenic	0.019	Stabilizing	0.966	D	0.525	neutral	N	0.461595651	None	None	N
A/Q	0.376	ambiguous	0.3224	benign	-0.604	Destabilizing	0.949	D	0.529	neutral	None	None	None	None	N
A/R	0.4397	ambiguous	0.3654	ambiguous	-0.548	Destabilizing	0.904	D	0.517	neutral	None	None	None	None	N
A/S	0.099	likely_benign	0.0933	benign	-1.009	Destabilizing	0.062	N	0.249	neutral	N	0.370146927	None	None	N
A/T	0.0899	likely_benign	0.0848	benign	-0.849	Destabilizing	0.022	N	0.231	neutral	N	0.368815989	None	None	N
A/V	0.1187	likely_benign	0.1088	benign	0.019	Stabilizing	0.012	N	0.361	neutral	N	0.383574798	None	None	N
A/W	0.7473	likely_pathogenic	0.712	pathogenic	-0.908	Destabilizing	0.998	D	0.66	neutral	None	None	None	None	N
A/Y	0.4388	ambiguous	0.3942	ambiguous	-0.391	Destabilizing	0.974	D	0.574	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.