TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3281	10066;10067;10068	chr2:178764674;178764673;178764672	chr2:179629401;179629400;179629399
N2AB	3281	10066;10067;10068	chr2:178764674;178764673;178764672	chr2:179629401;179629400;179629399
N2A	3281	10066;10067;10068	chr2:178764674;178764673;178764672	chr2:179629401;179629400;179629399
N2B	3235	9928;9929;9930	chr2:178764674;178764673;178764672	chr2:179629401;179629400;179629399
Novex-1	3235	9928;9929;9930	chr2:178764674;178764673;178764672	chr2:179629401;179629400;179629399
Novex-2	3235	9928;9929;9930	chr2:178764674;178764673;178764672	chr2:179629401;179629400;179629399
Novex-3	3281	10066;10067;10068	chr2:178764674;178764673;178764672	chr2:179629401;179629400;179629399

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-23
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.6204
• 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
T/A	None	None	None	N	0.119	0.156	0.18995819373	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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
T/A	0.0678	likely_benign	0.092	benign	-0.406	Destabilizing	None	N	0.119	neutral	N	0.423258884	None	None	I
T/C	0.5473	ambiguous	0.6699	pathogenic	-0.304	Destabilizing	0.859	D	0.335	neutral	None	None	None	None	I
T/D	0.4499	ambiguous	0.6073	pathogenic	0.472	Stabilizing	0.22	N	0.301	neutral	None	None	None	None	I
T/E	0.3399	likely_benign	0.4879	ambiguous	0.403	Stabilizing	0.104	N	0.303	neutral	None	None	None	None	I
T/F	0.3948	ambiguous	0.6229	pathogenic	-0.945	Destabilizing	0.497	N	0.415	neutral	None	None	None	None	I
T/G	0.2446	likely_benign	0.3389	benign	-0.524	Destabilizing	0.055	N	0.275	neutral	None	None	None	None	I
T/H	0.3102	likely_benign	0.4518	ambiguous	-0.744	Destabilizing	0.859	D	0.34	neutral	None	None	None	None	I
T/I	0.24	likely_benign	0.4675	ambiguous	-0.214	Destabilizing	0.001	N	0.26	neutral	N	0.501054178	None	None	I
T/K	0.285	likely_benign	0.4287	ambiguous	-0.214	Destabilizing	0.104	N	0.301	neutral	None	None	None	None	I
T/L	0.1253	likely_benign	0.2185	benign	-0.214	Destabilizing	0.02	N	0.291	neutral	None	None	None	None	I
T/M	0.1071	likely_benign	0.1699	benign	-0.148	Destabilizing	0.497	N	0.326	neutral	None	None	None	None	I
T/N	0.1535	likely_benign	0.2329	benign	-0.044	Destabilizing	0.175	N	0.163	neutral	N	0.430750986	None	None	I
T/P	0.063	likely_benign	0.0887	benign	-0.25	Destabilizing	None	N	0.172	neutral	N	0.418838892	None	None	I
T/Q	0.2454	likely_benign	0.3556	ambiguous	-0.218	Destabilizing	0.364	N	0.424	neutral	None	None	None	None	I
T/R	0.2156	likely_benign	0.3527	ambiguous	0.014	Stabilizing	0.364	N	0.387	neutral	None	None	None	None	I
T/S	0.1018	likely_benign	0.1332	benign	-0.296	Destabilizing	0.001	N	0.128	neutral	N	0.428212664	None	None	I
T/V	0.1721	likely_benign	0.296	benign	-0.25	Destabilizing	0.02	N	0.18	neutral	None	None	None	None	I
T/W	0.7204	likely_pathogenic	0.8442	pathogenic	-0.959	Destabilizing	0.958	D	0.34	neutral	None	None	None	None	I
T/Y	0.4509	ambiguous	0.6233	pathogenic	-0.656	Destabilizing	0.667	D	0.385	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.