TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5714	17365;17366;17367	chr2:178731735;178731734;178731733	chr2:179596462;179596461;179596460
N2AB	5397	16414;16415;16416	chr2:178731735;178731734;178731733	chr2:179596462;179596461;179596460
N2A	4470	13633;13634;13635	chr2:178731735;178731734;178731733	chr2:179596462;179596461;179596460
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-40
• Domain position: 78
• Structural Position: 162
• Q(SASA): 0.9978
• 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/G	rs772995909	0.017	0.351	N	0.384	0.159	0.355865052028	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
E/G	rs772995909	0.017	0.351	N	0.384	0.159	0.355865052028	gnomAD-4.0.0	1.36862E-06	None	None	None	None	I	None	0	0	None	0	2.52029E-05	None	0	0	8.99567E-07	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
E/A	0.2245	likely_benign	0.2018	benign	-0.037	Destabilizing	0.101	N	0.403	neutral	N	0.48186272	None	None	I
E/C	0.9411	likely_pathogenic	0.9352	pathogenic	-0.163	Destabilizing	0.951	D	0.345	neutral	None	None	None	None	I
E/D	0.1169	likely_benign	0.1141	benign	-0.355	Destabilizing	0.001	N	0.19	neutral	N	0.460564728	None	None	I
E/F	0.8942	likely_pathogenic	0.8917	pathogenic	-0.11	Destabilizing	0.716	D	0.375	neutral	None	None	None	None	I
E/G	0.2954	likely_benign	0.26	benign	-0.142	Destabilizing	0.351	N	0.384	neutral	N	0.475379465	None	None	I
E/H	0.6609	likely_pathogenic	0.635	pathogenic	0.471	Stabilizing	0.836	D	0.377	neutral	None	None	None	None	I
E/I	0.547	ambiguous	0.5485	ambiguous	0.18	Stabilizing	0.01	N	0.339	neutral	None	None	None	None	I
E/K	0.2805	likely_benign	0.2565	benign	0.411	Stabilizing	0.351	N	0.393	neutral	N	0.494733229	None	None	I
E/L	0.6291	likely_pathogenic	0.6067	pathogenic	0.18	Stabilizing	0.129	N	0.377	neutral	None	None	None	None	I
E/M	0.6445	likely_pathogenic	0.6412	pathogenic	-0.004	Destabilizing	0.716	D	0.381	neutral	None	None	None	None	I
E/N	0.3788	ambiguous	0.3579	ambiguous	0.185	Stabilizing	0.004	N	0.195	neutral	None	None	None	None	I
E/P	0.7212	likely_pathogenic	0.6261	pathogenic	0.125	Stabilizing	0.836	D	0.439	neutral	None	None	None	None	I
E/Q	0.2584	likely_benign	0.2377	benign	0.188	Stabilizing	0.523	D	0.384	neutral	N	0.483556231	None	None	I
E/R	0.443	ambiguous	0.4107	ambiguous	0.611	Stabilizing	0.836	D	0.375	neutral	None	None	None	None	I
E/S	0.2946	likely_benign	0.2694	benign	0.055	Stabilizing	0.228	N	0.377	neutral	None	None	None	None	I
E/T	0.3592	ambiguous	0.3423	ambiguous	0.15	Stabilizing	0.418	N	0.415	neutral	None	None	None	None	I
E/V	0.3494	ambiguous	0.3396	benign	0.125	Stabilizing	0.002	N	0.264	neutral	N	0.517650161	None	None	I
E/W	0.9658	likely_pathogenic	0.9607	pathogenic	-0.074	Destabilizing	0.983	D	0.429	neutral	None	None	None	None	I
E/Y	0.7994	likely_pathogenic	0.7909	pathogenic	0.109	Stabilizing	0.836	D	0.401	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.