TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24513	73762;73763;73764	chr2:178572595;178572594;178572593	chr2:179437322;179437321;179437320
N2AB	22872	68839;68840;68841	chr2:178572595;178572594;178572593	chr2:179437322;179437321;179437320
N2A	21945	66058;66059;66060	chr2:178572595;178572594;178572593	chr2:179437322;179437321;179437320
N2B	15448	46567;46568;46569	chr2:178572595;178572594;178572593	chr2:179437322;179437321;179437320
Novex-1	15573	46942;46943;46944	chr2:178572595;178572594;178572593	chr2:179437322;179437321;179437320
Novex-2	15640	47143;47144;47145	chr2:178572595;178572594;178572593	chr2:179437322;179437321;179437320
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-132
• Domain position: 83
• Structural Position: 173
• Q(SASA): 0.3443
• 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
N/S	rs1195528043	-0.685	0.034	N	0.157	0.068	0.188950314367	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	0	None	0	1.67823E-04	None	0	None	0	0	0
N/S	rs1195528043	-0.685	0.034	N	0.157	0.068	0.188950314367	gnomAD-4.0.0	4.10614E-06	None	None	None	None	I	None	0	0	None	0	1.51416E-04	None	0	0	0	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
N/A	0.2692	likely_benign	0.3091	benign	-1.14	Destabilizing	0.415	N	0.591	neutral	None	None	None	None	I
N/C	0.3152	likely_benign	0.3529	ambiguous	-0.179	Destabilizing	0.996	D	0.704	prob.neutral	None	None	None	None	I
N/D	0.487	ambiguous	0.4389	ambiguous	-0.456	Destabilizing	0.722	D	0.45	neutral	N	0.483819906	None	None	I
N/E	0.7887	likely_pathogenic	0.7808	pathogenic	-0.307	Destabilizing	0.775	D	0.459	neutral	None	None	None	None	I
N/F	0.6342	likely_pathogenic	0.6985	pathogenic	-0.719	Destabilizing	0.923	D	0.726	prob.delet.	None	None	None	None	I
N/G	0.4348	ambiguous	0.4497	ambiguous	-1.515	Destabilizing	0.633	D	0.426	neutral	None	None	None	None	I
N/H	0.1693	likely_benign	0.1722	benign	-0.97	Destabilizing	0.949	D	0.518	neutral	D	0.528229728	None	None	I
N/I	0.1946	likely_benign	0.272	benign	-0.158	Destabilizing	0.008	N	0.426	neutral	N	0.520148962	None	None	I
N/K	0.7492	likely_pathogenic	0.7102	pathogenic	-0.15	Destabilizing	0.565	D	0.466	neutral	N	0.484572164	None	None	I
N/L	0.2229	likely_benign	0.2903	benign	-0.158	Destabilizing	0.372	N	0.613	neutral	None	None	None	None	I
N/M	0.2703	likely_benign	0.3393	benign	0.17	Stabilizing	0.979	D	0.686	prob.neutral	None	None	None	None	I
N/P	0.6892	likely_pathogenic	0.7079	pathogenic	-0.457	Destabilizing	0.961	D	0.693	prob.neutral	None	None	None	None	I
N/Q	0.5693	likely_pathogenic	0.5775	pathogenic	-0.709	Destabilizing	0.923	D	0.511	neutral	None	None	None	None	I
N/R	0.76	likely_pathogenic	0.7193	pathogenic	-0.21	Destabilizing	0.923	D	0.493	neutral	None	None	None	None	I
N/S	0.0858	likely_benign	0.087	benign	-0.982	Destabilizing	0.034	N	0.157	neutral	N	0.452633104	None	None	I
N/T	0.1159	likely_benign	0.134	benign	-0.621	Destabilizing	0.565	D	0.442	neutral	N	0.44588049	None	None	I
N/V	0.2028	likely_benign	0.2639	benign	-0.457	Destabilizing	0.372	N	0.611	neutral	None	None	None	None	I
N/W	0.8527	likely_pathogenic	0.8741	pathogenic	-0.385	Destabilizing	0.996	D	0.699	prob.neutral	None	None	None	None	I
N/Y	0.2842	likely_benign	0.305	benign	-0.185	Destabilizing	0.949	D	0.699	prob.neutral	N	0.496443659	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.