TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28045	84358;84359;84360	chr2:178561999;178561998;178561997	chr2:179426726;179426725;179426724
N2AB	26404	79435;79436;79437	chr2:178561999;178561998;178561997	chr2:179426726;179426725;179426724
N2A	25477	76654;76655;76656	chr2:178561999;178561998;178561997	chr2:179426726;179426725;179426724
N2B	18980	57163;57164;57165	chr2:178561999;178561998;178561997	chr2:179426726;179426725;179426724
Novex-1	19105	57538;57539;57540	chr2:178561999;178561998;178561997	chr2:179426726;179426725;179426724
Novex-2	19172	57739;57740;57741	chr2:178561999;178561998;178561997	chr2:179426726;179426725;179426724
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: Ig-142
• Domain position: 83
• Structural Position: 168
• Q(SASA): 0.4468
• 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/I	None	None	0.326	N	0.535	0.365	0.34854441366	gnomAD-4.0.0	6.84367E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99539E-07	0	0
T/R	rs774026360	-0.025	0.326	D	0.573	0.307	0.387042434762	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
T/R	rs774026360	-0.025	0.326	D	0.573	0.307	0.387042434762	gnomAD-4.0.0	6.84367E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15969E-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	0.0816	likely_benign	0.0882	benign	-0.552	Destabilizing	0.001	N	0.141	neutral	N	0.493952124	None	None	I
T/C	0.3233	likely_benign	0.3263	benign	-0.379	Destabilizing	0.972	D	0.562	neutral	None	None	None	None	I
T/D	0.3753	ambiguous	0.3978	ambiguous	0.094	Stabilizing	0.561	D	0.541	neutral	None	None	None	None	I
T/E	0.31	likely_benign	0.3213	benign	0.066	Stabilizing	0.39	N	0.525	neutral	None	None	None	None	I
T/F	0.231	likely_benign	0.2405	benign	-0.794	Destabilizing	0.818	D	0.573	neutral	None	None	None	None	I
T/G	0.3036	likely_benign	0.3168	benign	-0.765	Destabilizing	0.209	N	0.492	neutral	None	None	None	None	I
T/H	0.2306	likely_benign	0.2424	benign	-1.045	Destabilizing	0.965	D	0.543	neutral	None	None	None	None	I
T/I	0.1345	likely_benign	0.1265	benign	-0.096	Destabilizing	0.326	N	0.535	neutral	N	0.513577316	None	None	I
T/K	0.2119	likely_benign	0.2164	benign	-0.57	Destabilizing	0.003	N	0.279	neutral	N	0.484935996	None	None	I
T/L	0.1083	likely_benign	0.1099	benign	-0.096	Destabilizing	0.083	N	0.442	neutral	None	None	None	None	I
T/M	0.0938	likely_benign	0.0954	benign	0.027	Stabilizing	0.103	N	0.363	neutral	None	None	None	None	I
T/N	0.1337	likely_benign	0.1371	benign	-0.439	Destabilizing	0.561	D	0.468	neutral	None	None	None	None	I
T/P	0.2545	likely_benign	0.3157	benign	-0.216	Destabilizing	0.662	D	0.611	neutral	D	0.531681571	None	None	I
T/Q	0.2444	likely_benign	0.2533	benign	-0.584	Destabilizing	0.818	D	0.615	neutral	None	None	None	None	I
T/R	0.1688	likely_benign	0.1931	benign	-0.346	Destabilizing	0.326	N	0.573	neutral	D	0.536505281	None	None	I
T/S	0.1045	likely_benign	0.1071	benign	-0.681	Destabilizing	0.016	N	0.146	neutral	N	0.469221496	None	None	I
T/V	0.1049	likely_benign	0.0988	benign	-0.216	Destabilizing	0.017	N	0.175	neutral	None	None	None	None	I
T/W	0.612	likely_pathogenic	0.6313	pathogenic	-0.781	Destabilizing	0.991	D	0.565	neutral	None	None	None	None	I
T/Y	0.2779	likely_benign	0.2926	benign	-0.522	Destabilizing	0.901	D	0.561	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.