TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32132	96619;96620;96621	chr2:178543579;178543578;178543577	chr2:179408306;179408305;179408304
N2AB	30491	91696;91697;91698	chr2:178543579;178543578;178543577	chr2:179408306;179408305;179408304
N2A	29564	88915;88916;88917	chr2:178543579;178543578;178543577	chr2:179408306;179408305;179408304
N2B	23067	69424;69425;69426	chr2:178543579;178543578;178543577	chr2:179408306;179408305;179408304
Novex-1	23192	69799;69800;69801	chr2:178543579;178543578;178543577	chr2:179408306;179408305;179408304
Novex-2	23259	70000;70001;70002	chr2:178543579;178543578;178543577	chr2:179408306;179408305;179408304
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-122
• Domain position: 28
• Structural Position: 30
• Q(SASA): 0.3147
• Predicted PPI site: I

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
D/Y	None	None	1.0	N	0.621	0.467	0.694113019094	gnomAD-4.0.0	1.60406E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02883E-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
D/A	0.9175	likely_pathogenic	0.8889	pathogenic	-0.386	Destabilizing	1.0	D	0.717	prob.delet.	N	0.487297447	None	None	I
D/C	0.9861	likely_pathogenic	0.9815	pathogenic	-0.048	Destabilizing	1.0	D	0.644	neutral	None	None	None	None	I
D/E	0.8346	likely_pathogenic	0.8044	pathogenic	-0.636	Destabilizing	0.994	D	0.447	neutral	N	0.480029292	None	None	I
D/F	0.9881	likely_pathogenic	0.984	pathogenic	-0.336	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	I
D/G	0.9215	likely_pathogenic	0.8922	pathogenic	-0.673	Destabilizing	1.0	D	0.715	prob.delet.	N	0.488818384	None	None	I
D/H	0.9475	likely_pathogenic	0.9319	pathogenic	-0.672	Destabilizing	1.0	D	0.65	neutral	N	0.501060062	None	None	I
D/I	0.978	likely_pathogenic	0.9708	pathogenic	0.343	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	I
D/K	0.9831	likely_pathogenic	0.9804	pathogenic	-0.172	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
D/L	0.9706	likely_pathogenic	0.9596	pathogenic	0.343	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
D/M	0.9911	likely_pathogenic	0.9883	pathogenic	0.71	Stabilizing	1.0	D	0.635	neutral	None	None	None	None	I
D/N	0.469	ambiguous	0.3749	ambiguous	-0.466	Destabilizing	1.0	D	0.704	prob.neutral	D	0.524388841	None	None	I
D/P	0.9858	likely_pathogenic	0.9816	pathogenic	0.125	Stabilizing	0.998	D	0.742	deleterious	None	None	None	None	I
D/Q	0.9686	likely_pathogenic	0.9625	pathogenic	-0.377	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	I
D/R	0.977	likely_pathogenic	0.9721	pathogenic	-0.126	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
D/S	0.7102	likely_pathogenic	0.6211	pathogenic	-0.634	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
D/T	0.8908	likely_pathogenic	0.863	pathogenic	-0.411	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
D/V	0.9492	likely_pathogenic	0.9319	pathogenic	0.125	Stabilizing	1.0	D	0.695	prob.neutral	N	0.504173934	None	None	I
D/W	0.9972	likely_pathogenic	0.9964	pathogenic	-0.256	Destabilizing	1.0	D	0.642	neutral	None	None	None	None	I
D/Y	0.9262	likely_pathogenic	0.9023	pathogenic	-0.127	Destabilizing	1.0	D	0.621	neutral	N	0.510214322	None	None	I

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.