TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18264	55015;55016;55017	chr2:178603897;178603896;178603895	chr2:179468624;179468623;179468622
N2AB	16623	50092;50093;50094	chr2:178603897;178603896;178603895	chr2:179468624;179468623;179468622
N2A	15696	47311;47312;47313	chr2:178603897;178603896;178603895	chr2:179468624;179468623;179468622
N2B	9199	27820;27821;27822	chr2:178603897;178603896;178603895	chr2:179468624;179468623;179468622
Novex-1	9324	28195;28196;28197	chr2:178603897;178603896;178603895	chr2:179468624;179468623;179468622
Novex-2	9391	28396;28397;28398	chr2:178603897;178603896;178603895	chr2:179468624;179468623;179468622
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: Fn3-20
• Domain position: 99
• Structural Position: 127
• Q(SASA): 0.1848
• 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
E/A	None	None	None	N	0.118	0.095	0.104622674875	gnomAD-4.0.0	1.60669E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.44329E-05	0
E/K	rs1253287416	-0.696	0.001	N	0.398	0.079	0.186928172975	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
E/K	rs1253287416	-0.696	0.001	N	0.398	0.079	0.186928172975	gnomAD-4.0.0	4.12128E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.41686E-06	0	0
E/Q	rs1253287416	None	0.007	N	0.346	0.067	0.17258766438	gnomAD-4.0.0	2.74752E-06	None	None	None	None	N	None	0	0	None	0	2.53344E-05	None	0	0	9.02811E-07	1.16566E-05	1.6645E-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	0.0595	likely_benign	0.0594	benign	-0.531	Destabilizing	None	N	0.118	neutral	N	0.445037049	None	None	N
E/C	0.5289	ambiguous	0.4887	ambiguous	-0.456	Destabilizing	0.131	N	0.472	neutral	None	None	None	None	N
E/D	0.2779	likely_benign	0.2203	benign	-1.198	Destabilizing	0.007	N	0.365	neutral	N	0.42731808	None	None	N
E/F	0.5693	likely_pathogenic	0.5147	ambiguous	0.18	Stabilizing	0.004	N	0.467	neutral	None	None	None	None	N
E/G	0.2461	likely_benign	0.1796	benign	-0.926	Destabilizing	0.001	N	0.354	neutral	N	0.445903841	None	None	N
E/H	0.4743	ambiguous	0.3937	ambiguous	-0.132	Destabilizing	0.069	N	0.45	neutral	None	None	None	None	N
E/I	0.1578	likely_benign	0.1536	benign	0.55	Stabilizing	0.004	N	0.429	neutral	None	None	None	None	N
E/K	0.272	likely_benign	0.1952	benign	-0.693	Destabilizing	0.001	N	0.398	neutral	N	0.444863691	None	None	N
E/L	0.2765	likely_benign	0.2247	benign	0.55	Stabilizing	0.002	N	0.393	neutral	None	None	None	None	N
E/M	0.2593	likely_benign	0.2423	benign	0.835	Stabilizing	0.131	N	0.513	neutral	None	None	None	None	N
E/N	0.4009	ambiguous	0.3409	ambiguous	-1.209	Destabilizing	0.009	N	0.345	neutral	None	None	None	None	N
E/P	0.9077	likely_pathogenic	0.8505	pathogenic	0.212	Stabilizing	0.009	N	0.467	neutral	None	None	None	None	N
E/Q	0.1597	likely_benign	0.1306	benign	-1.015	Destabilizing	0.007	N	0.346	neutral	N	0.444516974	None	None	N
E/R	0.3579	ambiguous	0.2633	benign	-0.376	Destabilizing	None	N	0.162	neutral	None	None	None	None	N
E/S	0.1596	likely_benign	0.1461	benign	-1.5	Destabilizing	0.002	N	0.373	neutral	None	None	None	None	N
E/T	0.1211	likely_benign	0.1124	benign	-1.174	Destabilizing	None	N	0.178	neutral	None	None	None	None	N
E/V	0.0811	likely_benign	0.0845	benign	0.212	Stabilizing	0.001	N	0.355	neutral	N	0.443823541	None	None	N
E/W	0.8904	likely_pathogenic	0.827	pathogenic	0.367	Stabilizing	0.131	N	0.457	neutral	None	None	None	None	N
E/Y	0.5224	ambiguous	0.4709	ambiguous	0.404	Stabilizing	None	N	0.235	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.