TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6517	19774;19775;19776	chr2:178728275;178728274;178728273	chr2:179593002;179593001;179593000
N2AB	6200	18823;18824;18825	chr2:178728275;178728274;178728273	chr2:179593002;179593001;179593000
N2A	5273	16042;16043;16044	chr2:178728275;178728274;178728273	chr2:179593002;179593001;179593000
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-49
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.7615
• 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
D/G	rs904836264	None	0.434	N	0.373	0.333	0.18274738541	gnomAD-4.0.0	1.36884E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99653E-07	0	1.65755E-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	0.4226	ambiguous	0.474	ambiguous	-0.405	Destabilizing	0.996	D	0.641	neutral	N	0.499225367	None	None	N
D/C	0.8763	likely_pathogenic	0.8836	pathogenic	-0.078	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	N
D/E	0.4268	ambiguous	0.4548	ambiguous	-0.302	Destabilizing	0.999	D	0.507	neutral	N	0.50644808	None	None	N
D/F	0.8666	likely_pathogenic	0.8804	pathogenic	-0.125	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
D/G	0.2436	likely_benign	0.2684	benign	-0.65	Destabilizing	0.434	N	0.373	neutral	N	0.472545829	None	None	N
D/H	0.6338	likely_pathogenic	0.6804	pathogenic	-0.036	Destabilizing	1.0	D	0.663	neutral	N	0.511088651	None	None	N
D/I	0.8567	likely_pathogenic	0.8793	pathogenic	0.21	Stabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
D/K	0.7766	likely_pathogenic	0.811	pathogenic	0.191	Stabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
D/L	0.7857	likely_pathogenic	0.8131	pathogenic	0.21	Stabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
D/M	0.9119	likely_pathogenic	0.9275	pathogenic	0.385	Stabilizing	1.0	D	0.672	neutral	None	None	None	None	N
D/N	0.1387	likely_benign	0.1599	benign	-0.244	Destabilizing	0.999	D	0.684	prob.neutral	N	0.461344935	None	None	N
D/P	0.9873	likely_pathogenic	0.9883	pathogenic	0.028	Stabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
D/Q	0.7251	likely_pathogenic	0.7767	pathogenic	-0.159	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
D/R	0.7666	likely_pathogenic	0.7923	pathogenic	0.403	Stabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
D/S	0.3081	likely_benign	0.3612	ambiguous	-0.368	Destabilizing	0.997	D	0.651	neutral	None	None	None	None	N
D/T	0.746	likely_pathogenic	0.7882	pathogenic	-0.164	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
D/V	0.6342	likely_pathogenic	0.6769	pathogenic	0.028	Stabilizing	1.0	D	0.681	prob.neutral	D	0.529446396	None	None	N
D/W	0.9654	likely_pathogenic	0.9673	pathogenic	0.08	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
D/Y	0.4099	ambiguous	0.4263	ambiguous	0.13	Stabilizing	1.0	D	0.675	prob.neutral	N	0.518090091	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.