TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24796	74611;74612;74613	chr2:178571746;178571745;178571744	chr2:179436473;179436472;179436471
N2AB	23155	69688;69689;69690	chr2:178571746;178571745;178571744	chr2:179436473;179436472;179436471
N2A	22228	66907;66908;66909	chr2:178571746;178571745;178571744	chr2:179436473;179436472;179436471
N2B	15731	47416;47417;47418	chr2:178571746;178571745;178571744	chr2:179436473;179436472;179436471
Novex-1	15856	47791;47792;47793	chr2:178571746;178571745;178571744	chr2:179436473;179436472;179436471
Novex-2	15923	47992;47993;47994	chr2:178571746;178571745;178571744	chr2:179436473;179436472;179436471
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-133
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.5096
• Predicted PPI site: I

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	None	None	0.822	N	0.436	0.232	0.386071988338	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/Q	None	None	0.97	N	0.456	0.332	0.3691244813	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
E/A	0.154	likely_benign	0.1539	benign	-0.686	Destabilizing	0.058	N	0.251	neutral	N	0.502680709	None	None	I
E/C	0.8025	likely_pathogenic	0.8071	pathogenic	-0.26	Destabilizing	0.998	D	0.644	neutral	None	None	None	None	I
E/D	0.1438	likely_benign	0.1539	benign	-0.709	Destabilizing	0.822	D	0.436	neutral	N	0.492800035	None	None	I
E/F	0.7236	likely_pathogenic	0.7352	pathogenic	-0.39	Destabilizing	0.956	D	0.639	neutral	None	None	None	None	I
E/G	0.2058	likely_benign	0.2034	benign	-0.945	Destabilizing	0.822	D	0.569	neutral	N	0.500143869	None	None	I
E/H	0.4028	ambiguous	0.4143	ambiguous	-0.333	Destabilizing	0.998	D	0.448	neutral	None	None	None	None	I
E/I	0.2965	likely_benign	0.299	benign	-0.012	Destabilizing	0.754	D	0.578	neutral	None	None	None	None	I
E/K	0.1371	likely_benign	0.1378	benign	-0.018	Destabilizing	0.822	D	0.447	neutral	N	0.458521713	None	None	I
E/L	0.394	ambiguous	0.3971	ambiguous	-0.012	Destabilizing	0.754	D	0.573	neutral	None	None	None	None	I
E/M	0.3736	ambiguous	0.374	ambiguous	0.207	Stabilizing	0.994	D	0.627	neutral	None	None	None	None	I
E/N	0.2337	likely_benign	0.24	benign	-0.445	Destabilizing	0.956	D	0.431	neutral	None	None	None	None	I
E/P	0.851	likely_pathogenic	0.8798	pathogenic	-0.216	Destabilizing	0.978	D	0.523	neutral	None	None	None	None	I
E/Q	0.1299	likely_benign	0.1307	benign	-0.397	Destabilizing	0.97	D	0.456	neutral	N	0.487268539	None	None	I
E/R	0.2826	likely_benign	0.2888	benign	0.245	Stabilizing	0.978	D	0.439	neutral	None	None	None	None	I
E/S	0.1539	likely_benign	0.1556	benign	-0.635	Destabilizing	0.754	D	0.399	neutral	None	None	None	None	I
E/T	0.1482	likely_benign	0.1475	benign	-0.423	Destabilizing	0.076	N	0.275	neutral	None	None	None	None	I
E/V	0.175	likely_benign	0.1777	benign	-0.216	Destabilizing	0.014	N	0.398	neutral	N	0.486812554	None	None	I
E/W	0.9102	likely_pathogenic	0.9179	pathogenic	-0.154	Destabilizing	0.998	D	0.685	prob.neutral	None	None	None	None	I
E/Y	0.6177	likely_pathogenic	0.6285	pathogenic	-0.129	Destabilizing	0.978	D	0.63	neutral	None	None	None	None	I

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.