TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19629	59110;59111;59112	chr2:178593323;178593322;178593321	chr2:179458050;179458049;179458048
N2AB	17988	54187;54188;54189	chr2:178593323;178593322;178593321	chr2:179458050;179458049;179458048
N2A	17061	51406;51407;51408	chr2:178593323;178593322;178593321	chr2:179458050;179458049;179458048
N2B	10564	31915;31916;31917	chr2:178593323;178593322;178593321	chr2:179458050;179458049;179458048
Novex-1	10689	32290;32291;32292	chr2:178593323;178593322;178593321	chr2:179458050;179458049;179458048
Novex-2	10756	32491;32492;32493	chr2:178593323;178593322;178593321	chr2:179458050;179458049;179458048
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-30
• Domain position: 51
• Structural Position: 69
• Q(SASA): 0.0993
• 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
T/A	None	None	None	N	0.147	0.093	0.12205267543	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05
T/S	rs1417896313	-1.174	0.001	N	0.151	0.099	0.115124310173	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
T/S	rs1417896313	-1.174	0.001	N	0.151	0.099	0.115124310173	gnomAD-4.0.0	1.3687E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79923E-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	0.1633	likely_benign	0.1536	benign	-0.804	Destabilizing	None	N	0.147	neutral	N	0.47650168	None	None	N
T/C	0.4403	ambiguous	0.4298	ambiguous	-0.547	Destabilizing	0.667	D	0.427	neutral	None	None	None	None	N
T/D	0.6884	likely_pathogenic	0.6592	pathogenic	0.044	Stabilizing	0.22	N	0.381	neutral	None	None	None	None	N
T/E	0.7255	likely_pathogenic	0.6829	pathogenic	0.085	Stabilizing	0.055	N	0.374	neutral	None	None	None	None	N
T/F	0.6218	likely_pathogenic	0.6104	pathogenic	-0.984	Destabilizing	0.497	N	0.44	neutral	None	None	None	None	N
T/G	0.2748	likely_benign	0.2657	benign	-1.062	Destabilizing	None	N	0.303	neutral	None	None	None	None	N
T/H	0.4936	ambiguous	0.4756	ambiguous	-1.181	Destabilizing	0.667	D	0.44	neutral	None	None	None	None	N
T/I	0.5011	ambiguous	0.4972	ambiguous	-0.204	Destabilizing	0.096	N	0.373	neutral	N	0.513961203	None	None	N
T/K	0.6236	likely_pathogenic	0.5682	pathogenic	-0.471	Destabilizing	0.055	N	0.367	neutral	None	None	None	None	N
T/L	0.2557	likely_benign	0.2428	benign	-0.204	Destabilizing	0.001	N	0.239	neutral	None	None	None	None	N
T/M	0.1946	likely_benign	0.1781	benign	-0.239	Destabilizing	0.497	N	0.452	neutral	None	None	None	None	N
T/N	0.1574	likely_benign	0.1569	benign	-0.578	Destabilizing	0.096	N	0.353	neutral	N	0.399462262	None	None	N
T/P	0.6798	likely_pathogenic	0.6235	pathogenic	-0.373	Destabilizing	0.301	N	0.441	neutral	N	0.470233603	None	None	N
T/Q	0.4857	ambiguous	0.4524	ambiguous	-0.573	Destabilizing	0.011	N	0.261	neutral	None	None	None	None	N
T/R	0.5472	ambiguous	0.4903	ambiguous	-0.358	Destabilizing	0.001	N	0.263	neutral	None	None	None	None	N
T/S	0.1132	likely_benign	0.1173	benign	-0.87	Destabilizing	0.001	N	0.151	neutral	N	0.444175831	None	None	N
T/V	0.3397	likely_benign	0.3399	benign	-0.373	Destabilizing	0.004	N	0.165	neutral	None	None	None	None	N
T/W	0.8499	likely_pathogenic	0.8348	pathogenic	-0.998	Destabilizing	0.958	D	0.453	neutral	None	None	None	None	N
T/Y	0.6323	likely_pathogenic	0.6222	pathogenic	-0.702	Destabilizing	0.667	D	0.44	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.