TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25854	77785;77786;77787	chr2:178568572;178568571;178568570	chr2:179433299;179433298;179433297
N2AB	24213	72862;72863;72864	chr2:178568572;178568571;178568570	chr2:179433299;179433298;179433297
N2A	23286	70081;70082;70083	chr2:178568572;178568571;178568570	chr2:179433299;179433298;179433297
N2B	16789	50590;50591;50592	chr2:178568572;178568571;178568570	chr2:179433299;179433298;179433297
Novex-1	16914	50965;50966;50967	chr2:178568572;178568571;178568570	chr2:179433299;179433298;179433297
Novex-2	16981	51166;51167;51168	chr2:178568572;178568571;178568570	chr2:179433299;179433298;179433297
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-136
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.1406
• 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	rs886055245	-0.126	None	N	0.342	0.17	0.277730125212	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
T/I	rs886055245	-0.126	None	N	0.342	0.17	0.277730125212	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	rs886055245	-0.126	None	N	0.342	0.17	0.277730125212	gnomAD-4.0.0	2.56333E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78822E-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	0.0841	likely_benign	0.0832	benign	-1.12	Destabilizing	0.027	N	0.561	neutral	N	0.5169008	None	None	N
T/C	0.2293	likely_benign	0.232	benign	-1.148	Destabilizing	0.824	D	0.583	neutral	None	None	None	None	N
T/D	0.4501	ambiguous	0.4178	ambiguous	-1.972	Destabilizing	0.555	D	0.65	neutral	None	None	None	None	N
T/E	0.277	likely_benign	0.2746	benign	-1.809	Destabilizing	0.555	D	0.648	neutral	None	None	None	None	N
T/F	0.1361	likely_benign	0.1323	benign	-0.946	Destabilizing	0.38	N	0.627	neutral	None	None	None	None	N
T/G	0.2357	likely_benign	0.2277	benign	-1.492	Destabilizing	0.262	N	0.645	neutral	None	None	None	None	N
T/H	0.1771	likely_benign	0.1711	benign	-1.707	Destabilizing	0.935	D	0.587	neutral	None	None	None	None	N
T/I	0.064	likely_benign	0.0682	benign	-0.164	Destabilizing	None	N	0.342	neutral	N	0.498277754	None	None	N
T/K	0.1785	likely_benign	0.1743	benign	-0.831	Destabilizing	0.484	N	0.651	neutral	N	0.459911367	None	None	N
T/L	0.0623	likely_benign	0.0635	benign	-0.164	Destabilizing	0.005	N	0.533	neutral	None	None	None	None	N
T/M	0.0703	likely_benign	0.0698	benign	-0.113	Destabilizing	0.38	N	0.614	neutral	None	None	None	None	N
T/N	0.1268	likely_benign	0.1187	benign	-1.524	Destabilizing	0.791	D	0.645	neutral	None	None	None	None	N
T/P	0.6905	likely_pathogenic	0.6782	pathogenic	-0.451	Destabilizing	0.484	N	0.632	neutral	N	0.517237847	None	None	N
T/Q	0.1816	likely_benign	0.1807	benign	-1.419	Destabilizing	0.791	D	0.635	neutral	None	None	None	None	N
T/R	0.145	likely_benign	0.1377	benign	-0.883	Destabilizing	0.484	N	0.641	neutral	N	0.515476648	None	None	N
T/S	0.0959	likely_benign	0.0913	benign	-1.64	Destabilizing	0.117	N	0.582	neutral	N	0.464623753	None	None	N
T/V	0.0582	likely_benign	0.0627	benign	-0.451	Destabilizing	None	N	0.193	neutral	None	None	None	None	N
T/W	0.4678	ambiguous	0.4235	ambiguous	-1.11	Destabilizing	0.935	D	0.625	neutral	None	None	None	None	N
T/Y	0.1817	likely_benign	0.1721	benign	-0.721	Destabilizing	0.555	D	0.633	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.