TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32505	97738;97739;97740	chr2:178541564;178541563;178541562	chr2:179406291;179406290;179406289
N2AB	30864	92815;92816;92817	chr2:178541564;178541563;178541562	chr2:179406291;179406290;179406289
N2A	29937	90034;90035;90036	chr2:178541564;178541563;178541562	chr2:179406291;179406290;179406289
N2B	23440	70543;70544;70545	chr2:178541564;178541563;178541562	chr2:179406291;179406290;179406289
Novex-1	23565	70918;70919;70920	chr2:178541564;178541563;178541562	chr2:179406291;179406290;179406289
Novex-2	23632	71119;71120;71121	chr2:178541564;178541563;178541562	chr2:179406291;179406290;179406289
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: Fn3-125
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.3171
• 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	rs747569584	0.043	0.971	N	0.641	0.308	0.304760801415	gnomAD-2.1.1	8.22E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.82E-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	0.071	likely_benign	0.0736	benign	-0.54	Destabilizing	0.489	N	0.457	neutral	N	0.414949002	None	None	N
T/C	0.3212	likely_benign	0.3414	ambiguous	-0.41	Destabilizing	0.998	D	0.631	neutral	None	None	None	None	N
T/D	0.1987	likely_benign	0.2234	benign	0.338	Stabilizing	0.956	D	0.577	neutral	None	None	None	None	N
T/E	0.1797	likely_benign	0.2092	benign	0.331	Stabilizing	0.86	D	0.547	neutral	None	None	None	None	N
T/F	0.1694	likely_benign	0.1956	benign	-0.666	Destabilizing	0.978	D	0.72	prob.delet.	None	None	None	None	N
T/G	0.1774	likely_benign	0.1775	benign	-0.766	Destabilizing	0.754	D	0.55	neutral	None	None	None	None	N
T/H	0.1676	likely_benign	0.1819	benign	-0.907	Destabilizing	0.994	D	0.699	prob.neutral	None	None	None	None	N
T/I	0.1248	likely_benign	0.1553	benign	-0.042	Destabilizing	0.971	D	0.641	neutral	N	0.439076656	None	None	N
T/K	0.1384	likely_benign	0.1726	benign	-0.446	Destabilizing	0.698	D	0.53	neutral	N	0.406137518	None	None	N
T/L	0.0879	likely_benign	0.0987	benign	-0.042	Destabilizing	0.86	D	0.531	neutral	None	None	None	None	N
T/M	0.0775	likely_benign	0.0815	benign	-0.096	Destabilizing	0.998	D	0.62	neutral	None	None	None	None	N
T/N	0.0725	likely_benign	0.0765	benign	-0.336	Destabilizing	0.915	D	0.51	neutral	None	None	None	None	N
T/P	0.0948	likely_benign	0.1101	benign	-0.176	Destabilizing	0.971	D	0.644	neutral	N	0.40962054	None	None	N
T/Q	0.1561	likely_benign	0.1721	benign	-0.436	Destabilizing	0.956	D	0.651	neutral	None	None	None	None	N
T/R	0.1269	likely_benign	0.1627	benign	-0.248	Destabilizing	0.032	N	0.312	neutral	N	0.375526609	None	None	N
T/S	0.0882	likely_benign	0.0891	benign	-0.632	Destabilizing	0.058	N	0.33	neutral	N	0.397960752	None	None	N
T/V	0.1037	likely_benign	0.1218	benign	-0.176	Destabilizing	0.86	D	0.5	neutral	None	None	None	None	N
T/W	0.4859	ambiguous	0.5253	ambiguous	-0.65	Destabilizing	0.998	D	0.732	prob.delet.	None	None	None	None	N
T/Y	0.1668	likely_benign	0.1886	benign	-0.39	Destabilizing	0.993	D	0.722	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.