TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33712	101359;101360;101361	chr2:178535481;178535480;178535479	chr2:179400208;179400207;179400206
N2AB	32071	96436;96437;96438	chr2:178535481;178535480;178535479	chr2:179400208;179400207;179400206
N2A	31144	93655;93656;93657	chr2:178535481;178535480;178535479	chr2:179400208;179400207;179400206
N2B	24647	74164;74165;74166	chr2:178535481;178535480;178535479	chr2:179400208;179400207;179400206
Novex-1	24772	74539;74540;74541	chr2:178535481;178535480;178535479	chr2:179400208;179400207;179400206
Novex-2	24839	74740;74741;74742	chr2:178535481;178535480;178535479	chr2:179400208;179400207;179400206
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: Fn3-132
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.6009
• 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	rs1060503937	-0.864	0.062	N	0.492	0.042	0.221734844693	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/D	rs1060503937	-0.864	0.062	N	0.492	0.042	0.221734844693	gnomAD-4.0.0	6.84207E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15931E-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	0.0807	likely_benign	0.0831	benign	-0.247	Destabilizing	0.001	N	0.245	neutral	N	0.378622843	None	None	N
E/C	0.8103	likely_pathogenic	0.8065	pathogenic	-0.271	Destabilizing	0.956	D	0.539	neutral	None	None	None	None	N
E/D	0.2254	likely_benign	0.2476	benign	-1.255	Destabilizing	0.062	N	0.492	neutral	N	0.519655025	None	None	N
E/F	0.7996	likely_pathogenic	0.7915	pathogenic	0.558	Stabilizing	0.915	D	0.545	neutral	None	None	None	None	N
E/G	0.1793	likely_benign	0.1888	benign	-0.653	Destabilizing	0.506	D	0.467	neutral	N	0.449909725	None	None	N
E/H	0.5924	likely_pathogenic	0.5828	pathogenic	0.424	Stabilizing	0.959	D	0.573	neutral	None	None	None	None	N
E/I	0.3646	ambiguous	0.3458	ambiguous	0.862	Stabilizing	0.712	D	0.577	neutral	None	None	None	None	N
E/K	0.1648	likely_benign	0.1475	benign	-0.241	Destabilizing	0.532	D	0.517	neutral	N	0.434401555	None	None	N
E/L	0.353	ambiguous	0.3695	ambiguous	0.862	Stabilizing	0.414	N	0.524	neutral	None	None	None	None	N
E/M	0.4447	ambiguous	0.4422	ambiguous	1.064	Stabilizing	0.912	D	0.537	neutral	None	None	None	None	N
E/N	0.3672	ambiguous	0.3905	ambiguous	-0.977	Destabilizing	0.7	D	0.573	neutral	None	None	None	None	N
E/P	0.1693	likely_benign	0.1901	benign	0.516	Stabilizing	None	N	0.246	neutral	None	None	None	None	N
E/Q	0.1508	likely_benign	0.1451	benign	-0.745	Destabilizing	0.623	D	0.548	neutral	N	0.43455627	None	None	N
E/R	0.3109	likely_benign	0.2656	benign	0.091	Stabilizing	0.915	D	0.571	neutral	None	None	None	None	N
E/S	0.1885	likely_benign	0.1987	benign	-1.22	Destabilizing	0.144	N	0.501	neutral	None	None	None	None	N
E/T	0.2224	likely_benign	0.2267	benign	-0.86	Destabilizing	0.529	D	0.503	neutral	None	None	None	None	N
E/V	0.2031	likely_benign	0.1903	benign	0.516	Stabilizing	0.159	N	0.511	neutral	N	0.459702644	None	None	N
E/W	0.9474	likely_pathogenic	0.9446	pathogenic	0.771	Stabilizing	0.997	D	0.631	neutral	None	None	None	None	N
E/Y	0.7072	likely_pathogenic	0.6939	pathogenic	0.829	Stabilizing	0.989	D	0.543	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.