TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28262	85009;85010;85011	chr2:178561348;178561347;178561346	chr2:179426075;179426074;179426073
N2AB	26621	80086;80087;80088	chr2:178561348;178561347;178561346	chr2:179426075;179426074;179426073
N2A	25694	77305;77306;77307	chr2:178561348;178561347;178561346	chr2:179426075;179426074;179426073
N2B	19197	57814;57815;57816	chr2:178561348;178561347;178561346	chr2:179426075;179426074;179426073
Novex-1	19322	58189;58190;58191	chr2:178561348;178561347;178561346	chr2:179426075;179426074;179426073
Novex-2	19389	58390;58391;58392	chr2:178561348;178561347;178561346	chr2:179426075;179426074;179426073
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: Fn3-94
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.3564
• 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/I	rs1703591532	None	0.014	N	0.262	0.134	0.242825505644	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/I	rs1703591532	None	0.014	N	0.262	0.134	0.242825505644	gnomAD-4.0.0	6.57514E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47024E-05	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	0.128	likely_benign	0.1365	benign	-0.608	Destabilizing	0.656	D	0.569	neutral	N	0.489718907	None	None	N
T/C	0.4717	ambiguous	0.4784	ambiguous	-0.366	Destabilizing	0.998	D	0.671	neutral	None	None	None	None	N
T/D	0.5755	likely_pathogenic	0.5779	pathogenic	0.234	Stabilizing	0.993	D	0.656	neutral	None	None	None	None	N
T/E	0.4166	ambiguous	0.4249	ambiguous	0.2	Stabilizing	0.993	D	0.598	neutral	None	None	None	None	N
T/F	0.3317	likely_benign	0.3269	benign	-0.86	Destabilizing	0.956	D	0.735	prob.delet.	None	None	None	None	N
T/G	0.3748	ambiguous	0.3889	ambiguous	-0.811	Destabilizing	0.978	D	0.623	neutral	None	None	None	None	N
T/H	0.4133	ambiguous	0.4234	ambiguous	-1.041	Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	N
T/I	0.1682	likely_benign	0.1689	benign	-0.178	Destabilizing	0.014	N	0.262	neutral	N	0.447890927	None	None	N
T/K	0.3415	ambiguous	0.3359	benign	-0.488	Destabilizing	0.97	D	0.606	neutral	N	0.485715809	None	None	N
T/L	0.1153	likely_benign	0.1122	benign	-0.178	Destabilizing	0.303	N	0.472	neutral	None	None	None	None	N
T/M	0.0971	likely_benign	0.0987	benign	-0.003	Destabilizing	0.559	D	0.423	neutral	None	None	None	None	N
T/N	0.219	likely_benign	0.2279	benign	-0.345	Destabilizing	0.993	D	0.577	neutral	None	None	None	None	N
T/P	0.5957	likely_pathogenic	0.6163	pathogenic	-0.29	Destabilizing	0.99	D	0.682	prob.neutral	N	0.493604551	None	None	N
T/Q	0.3319	likely_benign	0.3393	benign	-0.519	Destabilizing	0.978	D	0.673	neutral	None	None	None	None	N
T/R	0.2837	likely_benign	0.2863	benign	-0.235	Destabilizing	0.97	D	0.681	prob.neutral	N	0.472409196	None	None	N
T/S	0.1665	likely_benign	0.1706	benign	-0.633	Destabilizing	0.904	D	0.543	neutral	N	0.477266897	None	None	N
T/V	0.1401	likely_benign	0.138	benign	-0.29	Destabilizing	0.303	N	0.474	neutral	None	None	None	None	N
T/W	0.6559	likely_pathogenic	0.6562	pathogenic	-0.81	Destabilizing	0.998	D	0.775	deleterious	None	None	None	None	N
T/Y	0.4026	ambiguous	0.4034	ambiguous	-0.561	Destabilizing	0.978	D	0.729	prob.delet.	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.