TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8197	24814;24815;24816	chr2:178718517;178718516;178718515	chr2:179583244;179583243;179583242
N2AB	7880	23863;23864;23865	chr2:178718517;178718516;178718515	chr2:179583244;179583243;179583242
N2A	6953	21082;21083;21084	chr2:178718517;178718516;178718515	chr2:179583244;179583243;179583242
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-67
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.3961
• 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
T/I	rs748587371	-0.163	0.966	N	0.446	0.295	0.498001352042	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
T/I	rs748587371	-0.163	0.966	N	0.446	0.295	0.498001352042	gnomAD-4.0.0	8.21081E-06	None	None	None	None	N	None	0	0	None	0	2.51991E-05	None	0	0	8.99486E-06	0	1.65689E-05
T/K	rs748587371	-0.613	0.801	N	0.457	0.324	0.47558534428	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	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
T/A	0.1531	likely_benign	0.1416	benign	-0.273	Destabilizing	0.051	N	0.238	neutral	N	0.484465015	None	None	N
T/C	0.6758	likely_pathogenic	0.6247	pathogenic	-0.265	Destabilizing	0.998	D	0.455	neutral	None	None	None	None	N
T/D	0.4584	ambiguous	0.4985	ambiguous	0.047	Stabilizing	0.842	D	0.435	neutral	None	None	None	None	N
T/E	0.4743	ambiguous	0.461	ambiguous	-0.024	Destabilizing	0.842	D	0.462	neutral	None	None	None	None	N
T/F	0.3258	likely_benign	0.29	benign	-0.734	Destabilizing	0.974	D	0.57	neutral	None	None	None	None	N
T/G	0.4317	ambiguous	0.4021	ambiguous	-0.408	Destabilizing	0.728	D	0.545	neutral	None	None	None	None	N
T/H	0.3513	ambiguous	0.3535	ambiguous	-0.635	Destabilizing	0.081	N	0.517	neutral	None	None	None	None	N
T/I	0.3568	ambiguous	0.2892	benign	-0.038	Destabilizing	0.966	D	0.446	neutral	N	0.513935066	None	None	N
T/K	0.3793	ambiguous	0.3304	benign	-0.421	Destabilizing	0.801	D	0.457	neutral	N	0.493174748	None	None	N
T/L	0.1947	likely_benign	0.1639	benign	-0.038	Destabilizing	0.842	D	0.399	neutral	None	None	None	None	N
T/M	0.1329	likely_benign	0.1226	benign	-0.017	Destabilizing	0.998	D	0.429	neutral	None	None	None	None	N
T/N	0.153	likely_benign	0.1551	benign	-0.161	Destabilizing	0.842	D	0.397	neutral	None	None	None	None	N
T/P	0.4444	ambiguous	0.3835	ambiguous	-0.088	Destabilizing	0.012	N	0.321	neutral	N	0.507319438	None	None	N
T/Q	0.3494	ambiguous	0.3348	benign	-0.367	Destabilizing	0.974	D	0.441	neutral	None	None	None	None	N
T/R	0.3167	likely_benign	0.2882	benign	-0.126	Destabilizing	0.934	D	0.443	neutral	N	0.485478974	None	None	N
T/S	0.0984	likely_benign	0.1059	benign	-0.341	Destabilizing	0.051	N	0.273	neutral	N	0.473587166	None	None	N
T/V	0.2953	likely_benign	0.2427	benign	-0.088	Destabilizing	0.842	D	0.35	neutral	None	None	None	None	N
T/W	0.692	likely_pathogenic	0.6838	pathogenic	-0.78	Destabilizing	0.998	D	0.627	neutral	None	None	None	None	N
T/Y	0.3606	ambiguous	0.3332	benign	-0.491	Destabilizing	0.949	D	0.574	neutral	None	None	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.