TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24562	73909;73910;73911	chr2:178572448;178572447;178572446	chr2:179437175;179437174;179437173
N2AB	22921	68986;68987;68988	chr2:178572448;178572447;178572446	chr2:179437175;179437174;179437173
N2A	21994	66205;66206;66207	chr2:178572448;178572447;178572446	chr2:179437175;179437174;179437173
N2B	15497	46714;46715;46716	chr2:178572448;178572447;178572446	chr2:179437175;179437174;179437173
Novex-1	15622	47089;47090;47091	chr2:178572448;178572447;178572446	chr2:179437175;179437174;179437173
Novex-2	15689	47290;47291;47292	chr2:178572448;178572447;178572446	chr2:179437175;179437174;179437173
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-66
• Domain position: 44
• Structural Position: 54
• Q(SASA): 0.3299
• 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/R	None	None	0.993	N	0.429	0.399	0.401185642668	gnomAD-4.0.0	1.36961E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.32024E-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
T/A	0.2316	likely_benign	0.19	benign	-0.166	Destabilizing	0.139	N	0.441	neutral	N	0.481251352	None	None	N
T/C	0.8539	likely_pathogenic	0.8148	pathogenic	-0.37	Destabilizing	0.995	D	0.473	neutral	None	None	None	None	N
T/D	0.8899	likely_pathogenic	0.8499	pathogenic	0.026	Stabilizing	0.935	D	0.459	neutral	None	None	None	None	N
T/E	0.8455	likely_pathogenic	0.7967	pathogenic	-0.067	Destabilizing	0.979	D	0.459	neutral	None	None	None	None	N
T/F	0.7938	likely_pathogenic	0.7314	pathogenic	-0.828	Destabilizing	0.967	D	0.505	neutral	None	None	None	None	N
T/G	0.4639	ambiguous	0.3818	ambiguous	-0.219	Destabilizing	0.975	D	0.441	neutral	None	None	None	None	N
T/H	0.7387	likely_pathogenic	0.6588	pathogenic	-0.354	Destabilizing	0.996	D	0.541	neutral	None	None	None	None	N
T/I	0.7315	likely_pathogenic	0.6802	pathogenic	-0.148	Destabilizing	0.007	N	0.347	neutral	N	0.49098075	None	None	N
T/K	0.771	likely_pathogenic	0.6832	pathogenic	-0.263	Destabilizing	0.943	D	0.462	neutral	N	0.489081402	None	None	N
T/L	0.3492	ambiguous	0.294	benign	-0.148	Destabilizing	0.18	N	0.469	neutral	None	None	None	None	N
T/M	0.2925	likely_benign	0.2493	benign	-0.156	Destabilizing	0.976	D	0.437	neutral	None	None	None	None	N
T/N	0.4199	ambiguous	0.3525	ambiguous	-0.083	Destabilizing	0.935	D	0.41	neutral	None	None	None	None	N
T/P	0.5984	likely_pathogenic	0.4859	ambiguous	-0.131	Destabilizing	0.915	D	0.433	neutral	N	0.466862561	None	None	N
T/Q	0.6456	likely_pathogenic	0.5596	ambiguous	-0.294	Destabilizing	0.969	D	0.437	neutral	None	None	None	None	N
T/R	0.7482	likely_pathogenic	0.6457	pathogenic	0.033	Stabilizing	0.993	D	0.429	neutral	N	0.512342263	None	None	N
T/S	0.2166	likely_benign	0.1839	benign	-0.256	Destabilizing	0.247	N	0.423	neutral	N	0.441250169	None	None	N
T/V	0.5071	ambiguous	0.449	ambiguous	-0.131	Destabilizing	0.136	N	0.463	neutral	None	None	None	None	N
T/W	0.9575	likely_pathogenic	0.9346	pathogenic	-0.91	Destabilizing	0.999	D	0.62	neutral	None	None	None	None	N
T/Y	0.8688	likely_pathogenic	0.8148	pathogenic	-0.588	Destabilizing	0.983	D	0.513	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.