TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18329	55210;55211;55212	chr2:178602417;178602416;178602415	chr2:179467144;179467143;179467142
N2AB	16688	50287;50288;50289	chr2:178602417;178602416;178602415	chr2:179467144;179467143;179467142
N2A	15761	47506;47507;47508	chr2:178602417;178602416;178602415	chr2:179467144;179467143;179467142
N2B	9264	28015;28016;28017	chr2:178602417;178602416;178602415	chr2:179467144;179467143;179467142
Novex-1	9389	28390;28391;28392	chr2:178602417;178602416;178602415	chr2:179467144;179467143;179467142
Novex-2	9456	28591;28592;28593	chr2:178602417;178602416;178602415	chr2:179467144;179467143;179467142
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-21
• Domain position: 58
• Structural Position: 77
• Q(SASA): 0.1163
• 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
I/V	None	None	0.001	N	0.333	0.037	0.17948927462	gnomAD-4.0.0	1.3692E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79966E-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
I/A	0.4635	ambiguous	0.4297	ambiguous	-2.022	Highly Destabilizing	0.008	N	0.351	neutral	None	None	None	None	N
I/C	0.4975	ambiguous	0.4471	ambiguous	-1.182	Destabilizing	0.497	N	0.455	neutral	None	None	None	None	N
I/D	0.7608	likely_pathogenic	0.7051	pathogenic	-1.621	Destabilizing	0.085	N	0.445	neutral	None	None	None	None	N
I/E	0.6188	likely_pathogenic	0.5779	pathogenic	-1.469	Destabilizing	0.018	N	0.401	neutral	None	None	None	None	N
I/F	0.1121	likely_benign	0.0897	benign	-1.157	Destabilizing	None	N	0.144	neutral	None	None	None	None	N
I/G	0.7409	likely_pathogenic	0.6989	pathogenic	-2.501	Highly Destabilizing	0.037	N	0.41	neutral	None	None	None	None	N
I/H	0.3515	ambiguous	0.2819	benign	-1.805	Destabilizing	None	N	0.447	neutral	None	None	None	None	N
I/K	0.4625	ambiguous	0.4124	ambiguous	-1.344	Destabilizing	0.014	N	0.415	neutral	N	0.504405066	None	None	N
I/L	0.0779	likely_benign	0.077	benign	-0.692	Destabilizing	None	N	0.143	neutral	N	0.479565336	None	None	N
I/M	0.1014	likely_benign	0.0955	benign	-0.559	Destabilizing	0.017	N	0.471	neutral	N	0.510312318	None	None	N
I/N	0.2939	likely_benign	0.2578	benign	-1.44	Destabilizing	0.044	N	0.447	neutral	None	None	None	None	N
I/P	0.7717	likely_pathogenic	0.7638	pathogenic	-1.11	Destabilizing	0.22	N	0.511	neutral	None	None	None	None	N
I/Q	0.371	ambiguous	0.321	benign	-1.404	Destabilizing	0.085	N	0.515	neutral	None	None	None	None	N
I/R	0.3679	ambiguous	0.324	benign	-0.996	Destabilizing	0.033	N	0.466	neutral	N	0.473138033	None	None	N
I/S	0.3946	ambiguous	0.3592	ambiguous	-2.185	Highly Destabilizing	0.037	N	0.377	neutral	None	None	None	None	N
I/T	0.4041	ambiguous	0.3984	ambiguous	-1.896	Destabilizing	0.014	N	0.375	neutral	N	0.439796227	None	None	N
I/V	0.1037	likely_benign	0.0969	benign	-1.11	Destabilizing	0.001	N	0.333	neutral	N	0.405163578	None	None	N
I/W	0.5673	likely_pathogenic	0.5029	ambiguous	-1.425	Destabilizing	0.497	N	0.487	neutral	None	None	None	None	N
I/Y	0.3566	ambiguous	0.27	benign	-1.124	Destabilizing	0.009	N	0.37	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.