TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5071	15436;15437;15438	chr2:178734713;178734712;178734711	chr2:179599440;179599439;179599438
N2AB	4754	14485;14486;14487	chr2:178734713;178734712;178734711	chr2:179599440;179599439;179599438
N2A	3827	11704;11705;11706	chr2:178734713;178734712;178734711	chr2:179599440;179599439;179599438
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-33
• Domain position: 91
• Structural Position: 177
• Q(SASA): 0.1924
• 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/T	None	None	0.062	N	0.349	0.249	None	gnomAD-4.0.0	2.75503E-06	None	None	None	None	N	None	9.04159E-05	0	None	0	0	None	0	0	0	1.17454E-05	0
I/V	rs777480345	-1.433	None	N	0.151	0.084	0.124217242631	gnomAD-2.1.1	1.22E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.69E-05	0
I/V	rs777480345	-1.433	None	N	0.151	0.084	0.124217242631	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/V	rs777480345	-1.433	None	N	0.151	0.084	0.124217242631	gnomAD-4.0.0	1.2468E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	6.6379E-04	1.27848E-05	0	1.61223E-05

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	0.8616	likely_pathogenic	0.7815	pathogenic	-2.441	Highly Destabilizing	0.035	N	0.346	neutral	None	None	None	None	N
I/C	0.9257	likely_pathogenic	0.898	pathogenic	-1.673	Destabilizing	0.824	D	0.347	neutral	None	None	None	None	N
I/D	0.9954	likely_pathogenic	0.9935	pathogenic	-2.686	Highly Destabilizing	0.555	D	0.409	neutral	None	None	None	None	N
I/E	0.986	likely_pathogenic	0.981	pathogenic	-2.58	Highly Destabilizing	0.555	D	0.397	neutral	None	None	None	None	N
I/F	0.6387	likely_pathogenic	0.5936	pathogenic	-1.545	Destabilizing	0.317	N	0.367	neutral	D	0.541145959	None	None	N
I/G	0.9745	likely_pathogenic	0.9591	pathogenic	-2.864	Highly Destabilizing	0.262	N	0.334	neutral	None	None	None	None	N
I/H	0.9842	likely_pathogenic	0.977	pathogenic	-2.171	Highly Destabilizing	0.935	D	0.417	neutral	None	None	None	None	N
I/K	0.9723	likely_pathogenic	0.9635	pathogenic	-1.899	Destabilizing	0.555	D	0.394	neutral	None	None	None	None	N
I/L	0.3417	ambiguous	0.2928	benign	-1.266	Destabilizing	0.005	N	0.237	neutral	N	0.454862399	None	None	N
I/M	0.3019	likely_benign	0.2708	benign	-1.107	Destabilizing	0.317	N	0.407	neutral	N	0.499602707	None	None	N
I/N	0.9231	likely_pathogenic	0.8937	pathogenic	-1.941	Destabilizing	0.741	D	0.436	neutral	D	0.543041521	None	None	N
I/P	0.9805	likely_pathogenic	0.9713	pathogenic	-1.635	Destabilizing	0.555	D	0.423	neutral	None	None	None	None	N
I/Q	0.9711	likely_pathogenic	0.958	pathogenic	-2.013	Highly Destabilizing	0.791	D	0.431	neutral	None	None	None	None	N
I/R	0.9581	likely_pathogenic	0.941	pathogenic	-1.342	Destabilizing	0.555	D	0.429	neutral	None	None	None	None	N
I/S	0.8831	likely_pathogenic	0.8232	pathogenic	-2.549	Highly Destabilizing	0.117	N	0.323	neutral	N	0.500663741	None	None	N
I/T	0.7649	likely_pathogenic	0.6763	pathogenic	-2.331	Highly Destabilizing	0.062	N	0.349	neutral	N	0.446592436	None	None	N
I/V	0.0875	likely_benign	0.0785	benign	-1.635	Destabilizing	None	N	0.151	neutral	N	0.330124873	None	None	N
I/W	0.9869	likely_pathogenic	0.9843	pathogenic	-1.817	Destabilizing	0.935	D	0.467	neutral	None	None	None	None	N
I/Y	0.9555	likely_pathogenic	0.945	pathogenic	-1.605	Destabilizing	0.555	D	0.356	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.