TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18324	55195;55196;55197	chr2:178602432;178602431;178602430	chr2:179467159;179467158;179467157
N2AB	16683	50272;50273;50274	chr2:178602432;178602431;178602430	chr2:179467159;179467158;179467157
N2A	15756	47491;47492;47493	chr2:178602432;178602431;178602430	chr2:179467159;179467158;179467157
N2B	9259	28000;28001;28002	chr2:178602432;178602431;178602430	chr2:179467159;179467158;179467157
Novex-1	9384	28375;28376;28377	chr2:178602432;178602431;178602430	chr2:179467159;179467158;179467157
Novex-2	9451	28576;28577;28578	chr2:178602432;178602431;178602430	chr2:179467159;179467158;179467157
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: Fn3-21
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.3784
• 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/Q	None	None	0.98	N	0.431	0.208	0.297031009988	gnomAD-4.0.0	1.59372E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43361E-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	0.1255	likely_benign	0.1203	benign	-0.164	Destabilizing	0.98	D	0.455	neutral	N	0.464164314	None	None	N
E/C	0.7394	likely_pathogenic	0.7422	pathogenic	-0.013	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
E/D	0.0809	likely_benign	0.0802	benign	-0.221	Destabilizing	0.011	N	0.133	neutral	N	0.416893229	None	None	N
E/F	0.6161	likely_pathogenic	0.5978	pathogenic	-0.167	Destabilizing	0.999	D	0.621	neutral	None	None	None	None	N
E/G	0.1109	likely_benign	0.1061	benign	-0.324	Destabilizing	0.961	D	0.464	neutral	N	0.460953438	None	None	N
E/H	0.3397	likely_benign	0.3237	benign	0.209	Stabilizing	0.999	D	0.417	neutral	None	None	None	None	N
E/I	0.2693	likely_benign	0.248	benign	0.208	Stabilizing	0.999	D	0.601	neutral	None	None	None	None	N
E/K	0.1387	likely_benign	0.12	benign	0.391	Stabilizing	0.961	D	0.493	neutral	N	0.448485573	None	None	N
E/L	0.2829	likely_benign	0.267	benign	0.208	Stabilizing	0.996	D	0.594	neutral	None	None	None	None	N
E/M	0.3743	ambiguous	0.348	ambiguous	0.159	Stabilizing	1.0	D	0.579	neutral	None	None	None	None	N
E/N	0.1663	likely_benign	0.1662	benign	0.198	Stabilizing	0.97	D	0.439	neutral	None	None	None	None	N
E/P	0.2697	likely_benign	0.2568	benign	0.104	Stabilizing	0.999	D	0.418	neutral	None	None	None	None	N
E/Q	0.1237	likely_benign	0.1134	benign	0.216	Stabilizing	0.98	D	0.431	neutral	N	0.459067926	None	None	N
E/R	0.2418	likely_benign	0.2134	benign	0.593	Stabilizing	0.996	D	0.414	neutral	None	None	None	None	N
E/S	0.1421	likely_benign	0.1415	benign	0.025	Stabilizing	0.97	D	0.467	neutral	None	None	None	None	N
E/T	0.1694	likely_benign	0.1564	benign	0.154	Stabilizing	0.985	D	0.411	neutral	None	None	None	None	N
E/V	0.1705	likely_benign	0.1586	benign	0.104	Stabilizing	0.998	D	0.483	neutral	N	0.467257761	None	None	N
E/W	0.8356	likely_pathogenic	0.8237	pathogenic	-0.086	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/Y	0.4749	ambiguous	0.4572	ambiguous	0.064	Stabilizing	0.999	D	0.569	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.