TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32592	97999;98000;98001	chr2:178541303;178541302;178541301	chr2:179406030;179406029;179406028
N2AB	30951	93076;93077;93078	chr2:178541303;178541302;178541301	chr2:179406030;179406029;179406028
N2A	30024	90295;90296;90297	chr2:178541303;178541302;178541301	chr2:179406030;179406029;179406028
N2B	23527	70804;70805;70806	chr2:178541303;178541302;178541301	chr2:179406030;179406029;179406028
Novex-1	23652	71179;71180;71181	chr2:178541303;178541302;178541301	chr2:179406030;179406029;179406028
Novex-2	23719	71380;71381;71382	chr2:178541303;178541302;178541301	chr2:179406030;179406029;179406028
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-125
• Domain position: 94
• Structural Position: 127
• Q(SASA): 0.127
• 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
I/V	None	None	None	N	0.161	0.092	0.268211541103	gnomAD-4.0.0	1.46314E-06	None	None	None	None	N	None	3.17319E-05	0	None	0	0	None	0	0	0	1.35146E-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
I/A	0.0627	likely_benign	0.0877	benign	-1.931	Destabilizing	None	N	0.401	neutral	None	None	None	None	N
I/C	0.2797	likely_benign	0.3397	benign	-1.087	Destabilizing	0.204	N	0.581	neutral	None	None	None	None	N
I/D	0.3822	ambiguous	0.4954	ambiguous	-1.929	Destabilizing	0.035	N	0.68	prob.neutral	None	None	None	None	N
I/E	0.2515	likely_benign	0.3571	ambiguous	-1.858	Destabilizing	0.035	N	0.619	neutral	None	None	None	None	N
I/F	0.1096	likely_benign	0.1335	benign	-1.236	Destabilizing	0.026	N	0.547	neutral	N	0.515449644	None	None	N
I/G	0.267	likely_benign	0.3355	benign	-2.309	Highly Destabilizing	0.007	N	0.586	neutral	None	None	None	None	N
I/H	0.2386	likely_benign	0.3223	benign	-1.514	Destabilizing	0.439	N	0.687	prob.delet.	None	None	None	None	N
I/K	0.1717	likely_benign	0.2454	benign	-1.582	Destabilizing	0.035	N	0.613	neutral	None	None	None	None	N
I/L	0.0844	likely_benign	0.1007	benign	-0.921	Destabilizing	0.001	N	0.325	neutral	N	0.487684253	None	None	N
I/M	0.0613	likely_benign	0.071	benign	-0.678	Destabilizing	0.195	N	0.493	neutral	N	0.521722256	None	None	N
I/N	0.1261	likely_benign	0.1911	benign	-1.533	Destabilizing	0.026	N	0.71	prob.delet.	N	0.49517253	None	None	N
I/P	0.8063	likely_pathogenic	0.8732	pathogenic	-1.231	Destabilizing	0.068	N	0.699	prob.delet.	None	None	None	None	N
I/Q	0.178	likely_benign	0.2359	benign	-1.645	Destabilizing	0.204	N	0.765	deleterious	None	None	None	None	N
I/R	0.124	likely_benign	0.1836	benign	-0.964	Destabilizing	0.035	N	0.739	deleterious	None	None	None	None	N
I/S	0.0865	likely_benign	0.126	benign	-2.078	Highly Destabilizing	0.006	N	0.635	neutral	N	0.493905082	None	None	N
I/T	0.052	likely_benign	0.0723	benign	-1.893	Destabilizing	None	N	0.374	neutral	N	0.481788308	None	None	N
I/V	0.0554	likely_benign	0.0551	benign	-1.231	Destabilizing	None	N	0.161	neutral	N	0.414301215	None	None	N
I/W	0.5909	likely_pathogenic	0.6706	pathogenic	-1.432	Destabilizing	0.747	D	0.715	prob.delet.	None	None	None	None	N
I/Y	0.2784	likely_benign	0.3736	ambiguous	-1.196	Destabilizing	0.204	N	0.685	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.