TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17566	52921;52922;52923	chr2:178608187;178608186;178608185	chr2:179472914;179472913;179472912
N2AB	15925	47998;47999;48000	chr2:178608187;178608186;178608185	chr2:179472914;179472913;179472912
N2A	14998	45217;45218;45219	chr2:178608187;178608186;178608185	chr2:179472914;179472913;179472912
N2B	8501	25726;25727;25728	chr2:178608187;178608186;178608185	chr2:179472914;179472913;179472912
Novex-1	8626	26101;26102;26103	chr2:178608187;178608186;178608185	chr2:179472914;179472913;179472912
Novex-2	8693	26302;26303;26304	chr2:178608187;178608186;178608185	chr2:179472914;179472913;179472912
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: Fn3-15
• Domain position: 97
• Structural Position: 132
• Q(SASA): 1.3253
• 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/Y	None	None	0.004	N	0.381	0.227	0.262662153117	gnomAD-4.0.0	1.62105E-06	None	None	None	None	N	None	0	2.36485E-05	None	0	0	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
D/A	0.243	likely_benign	0.3426	ambiguous	-0.232	Destabilizing	0.003	N	0.263	neutral	N	0.467982906	None	None	N
D/C	0.7673	likely_pathogenic	0.8373	pathogenic	0.136	Stabilizing	0.984	D	0.449	neutral	None	None	None	None	N
D/E	0.2991	likely_benign	0.3919	ambiguous	-0.203	Destabilizing	0.189	N	0.491	neutral	N	0.474698234	None	None	N
D/F	0.7016	likely_pathogenic	0.8048	pathogenic	-0.331	Destabilizing	0.568	D	0.559	neutral	None	None	None	None	N
D/G	0.3844	ambiguous	0.538	ambiguous	-0.423	Destabilizing	0.104	N	0.47	neutral	N	0.491302482	None	None	N
D/H	0.444	ambiguous	0.538	ambiguous	-0.314	Destabilizing	0.664	D	0.457	neutral	N	0.461617143	None	None	N
D/I	0.527	ambiguous	0.6732	pathogenic	0.218	Stabilizing	0.724	D	0.547	neutral	None	None	None	None	N
D/K	0.5772	likely_pathogenic	0.7008	pathogenic	0.147	Stabilizing	0.428	N	0.628	neutral	None	None	None	None	N
D/L	0.4414	ambiguous	0.5853	pathogenic	0.218	Stabilizing	0.272	N	0.565	neutral	None	None	None	None	N
D/M	0.7355	likely_pathogenic	0.8391	pathogenic	0.433	Stabilizing	0.984	D	0.439	neutral	None	None	None	None	N
D/N	0.1621	likely_benign	0.1818	benign	0.062	Stabilizing	0.361	N	0.463	neutral	N	0.496612302	None	None	N
D/P	0.7494	likely_pathogenic	0.7938	pathogenic	0.09	Stabilizing	0.842	D	0.559	neutral	None	None	None	None	N
D/Q	0.5282	ambiguous	0.6607	pathogenic	0.092	Stabilizing	0.842	D	0.368	neutral	None	None	None	None	N
D/R	0.6263	likely_pathogenic	0.7436	pathogenic	0.248	Stabilizing	0.842	D	0.561	neutral	None	None	None	None	N
D/S	0.1951	likely_benign	0.2578	benign	-0.094	Destabilizing	0.028	N	0.35	neutral	None	None	None	None	N
D/T	0.4194	ambiguous	0.5539	ambiguous	0.043	Stabilizing	0.272	N	0.583	neutral	None	None	None	None	N
D/V	0.3437	ambiguous	0.4939	ambiguous	0.09	Stabilizing	0.361	N	0.561	neutral	N	0.460096206	None	None	N
D/W	0.9397	likely_pathogenic	0.963	pathogenic	-0.28	Destabilizing	0.953	D	0.493	neutral	None	None	None	None	N
D/Y	0.3002	likely_benign	0.4149	ambiguous	-0.132	Destabilizing	0.004	N	0.381	neutral	N	0.474935231	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.