TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8208	24847;24848;24849	chr2:178718484;178718483;178718482	chr2:179583211;179583210;179583209
N2AB	7891	23896;23897;23898	chr2:178718484;178718483;178718482	chr2:179583211;179583210;179583209
N2A	6964	21115;21116;21117	chr2:178718484;178718483;178718482	chr2:179583211;179583210;179583209
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-67
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.8527
• 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
E/K	rs190192954	0.453	0.331	N	0.26	0.261	None	gnomAD-2.1.1	5.72E-05	None	None	None	None	I	None	5.37412E-04	5.66E-05	None	0	0	None	0	None	0	7.83E-06	0
E/K	rs190192954	0.453	0.331	N	0.26	0.261	None	gnomAD-3.1.2	1.44645E-04	None	None	None	None	I	None	4.34573E-04	1.96515E-04	0	0	0	None	0	0	0	0	4.77555E-04
E/K	rs190192954	0.453	0.331	N	0.26	0.261	None	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
E/K	rs190192954	0.453	0.331	N	0.26	0.261	None	gnomAD-4.0.0	3.16047E-05	None	None	None	None	I	None	5.19986E-04	8.33361E-05	None	0	0	None	0	0	3.39064E-06	0	4.80215E-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
E/A	0.1174	likely_benign	0.1201	benign	-0.378	Destabilizing	0.001	N	0.168	neutral	N	0.504943783	None	None	I
E/C	0.709	likely_pathogenic	0.684	pathogenic	-0.375	Destabilizing	0.958	D	0.329	neutral	None	None	None	None	I
E/D	0.0771	likely_benign	0.0819	benign	-0.372	Destabilizing	None	N	0.102	neutral	N	0.448183636	None	None	I
E/F	0.6172	likely_pathogenic	0.6159	pathogenic	-0.098	Destabilizing	0.859	D	0.361	neutral	None	None	None	None	I
E/G	0.0682	likely_benign	0.0645	benign	-0.569	Destabilizing	None	N	0.15	neutral	N	0.323462127	None	None	I
E/H	0.2689	likely_benign	0.2815	benign	0.422	Stabilizing	0.859	D	0.293	neutral	None	None	None	None	I
E/I	0.3252	likely_benign	0.3286	benign	0.096	Stabilizing	0.667	D	0.412	neutral	None	None	None	None	I
E/K	0.079	likely_benign	0.077	benign	0.205	Stabilizing	0.331	N	0.26	neutral	N	0.510002886	None	None	I
E/L	0.3646	ambiguous	0.3677	ambiguous	0.096	Stabilizing	0.22	N	0.426	neutral	None	None	None	None	I
E/M	0.3726	ambiguous	0.3709	ambiguous	-0.035	Destabilizing	0.859	D	0.325	neutral	None	None	None	None	I
E/N	0.107	likely_benign	0.1138	benign	-0.267	Destabilizing	0.124	N	0.245	neutral	None	None	None	None	I
E/P	0.4474	ambiguous	0.4874	ambiguous	-0.043	Destabilizing	0.364	N	0.427	neutral	None	None	None	None	I
E/Q	0.1015	likely_benign	0.1045	benign	-0.202	Destabilizing	0.523	D	0.325	neutral	N	0.511043036	None	None	I
E/R	0.1427	likely_benign	0.143	benign	0.58	Stabilizing	0.364	N	0.294	neutral	None	None	None	None	I
E/S	0.1043	likely_benign	0.1065	benign	-0.409	Destabilizing	0.055	N	0.239	neutral	None	None	None	None	I
E/T	0.1409	likely_benign	0.1435	benign	-0.239	Destabilizing	0.22	N	0.331	neutral	None	None	None	None	I
E/V	0.2361	likely_benign	0.2385	benign	-0.043	Destabilizing	0.175	N	0.385	neutral	N	0.473088807	None	None	I
E/W	0.7686	likely_pathogenic	0.7698	pathogenic	0.092	Stabilizing	0.958	D	0.342	neutral	None	None	None	None	I
E/Y	0.427	ambiguous	0.4434	ambiguous	0.151	Stabilizing	0.859	D	0.345	neutral	None	None	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.