TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5797	17614;17615;17616	chr2:178731377;178731376;178731375	chr2:179596104;179596103;179596102
N2AB	5480	16663;16664;16665	chr2:178731377;178731376;178731375	chr2:179596104;179596103;179596102
N2A	4553	13882;13883;13884	chr2:178731377;178731376;178731375	chr2:179596104;179596103;179596102
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-41
• Domain position: 68
• Structural Position: 151
• Q(SASA): 0.3449
• 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/N	rs752644615	-0.601	0.801	N	0.439	0.154	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
D/N	rs752644615	-0.601	0.801	N	0.439	0.154	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
D/N	rs752644615	-0.601	0.801	N	0.439	0.154	None	gnomAD-4.0.0	6.57263E-06	None	None	None	None	N	None	2.41266E-05	0	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	0.1441	likely_benign	0.1211	benign	-0.631	Destabilizing	0.022	N	0.291	neutral	N	0.373268243	None	None	N
D/C	0.6553	likely_pathogenic	0.5783	pathogenic	-0.178	Destabilizing	0.998	D	0.564	neutral	None	None	None	None	N
D/E	0.243	likely_benign	0.213	benign	-0.537	Destabilizing	0.771	D	0.437	neutral	N	0.405801949	None	None	N
D/F	0.6726	likely_pathogenic	0.6171	pathogenic	-0.128	Destabilizing	0.991	D	0.599	neutral	None	None	None	None	N
D/G	0.1549	likely_benign	0.1371	benign	-0.976	Destabilizing	0.005	N	0.192	neutral	N	0.39510774	None	None	N
D/H	0.3334	likely_benign	0.2986	benign	-0.326	Destabilizing	0.997	D	0.561	neutral	N	0.485324312	None	None	N
D/I	0.5327	ambiguous	0.4586	ambiguous	0.281	Stabilizing	0.949	D	0.609	neutral	None	None	None	None	N
D/K	0.4951	ambiguous	0.4516	ambiguous	-0.11	Destabilizing	0.915	D	0.571	neutral	None	None	None	None	N
D/L	0.5011	ambiguous	0.4536	ambiguous	0.281	Stabilizing	0.842	D	0.566	neutral	None	None	None	None	N
D/M	0.7077	likely_pathogenic	0.6368	pathogenic	0.691	Stabilizing	0.998	D	0.563	neutral	None	None	None	None	N
D/N	0.1123	likely_benign	0.1061	benign	-0.688	Destabilizing	0.801	D	0.439	neutral	N	0.460292582	None	None	N
D/P	0.8894	likely_pathogenic	0.8722	pathogenic	0.001	Stabilizing	0.974	D	0.609	neutral	None	None	None	None	N
D/Q	0.3811	ambiguous	0.3436	ambiguous	-0.554	Destabilizing	0.991	D	0.529	neutral	None	None	None	None	N
D/R	0.4628	ambiguous	0.4257	ambiguous	0.064	Stabilizing	0.974	D	0.607	neutral	None	None	None	None	N
D/S	0.1045	likely_benign	0.0905	benign	-0.91	Destabilizing	0.525	D	0.441	neutral	None	None	None	None	N
D/T	0.2683	likely_benign	0.2261	benign	-0.615	Destabilizing	0.067	N	0.26	neutral	None	None	None	None	N
D/V	0.3302	likely_benign	0.2821	benign	0.001	Stabilizing	0.801	D	0.554	neutral	N	0.455270764	None	None	N
D/W	0.9208	likely_pathogenic	0.9009	pathogenic	0.139	Stabilizing	0.998	D	0.617	neutral	None	None	None	None	N
D/Y	0.2881	likely_benign	0.2557	benign	0.152	Stabilizing	0.989	D	0.577	neutral	N	0.485497671	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.