TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8850	26773;26774;26775	chr2:178714110;178714109;178714108	chr2:179578837;179578836;179578835
N2AB	8533	25822;25823;25824	chr2:178714110;178714109;178714108	chr2:179578837;179578836;179578835
N2A	7606	23041;23042;23043	chr2:178714110;178714109;178714108	chr2:179578837;179578836;179578835
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-74
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.6155
• 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/K	None	None	0.998	D	0.517	0.352	0.502691689211	gnomAD-4.0.0	6.84258E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9951E-07	0	0
E/Q	rs2077103240	None	0.999	N	0.629	0.292	0.441844919209	gnomAD-4.0.0	6.84258E-07	None	None	None	None	N	None	0	0	None	0	2.51978E-05	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
E/A	0.2566	likely_benign	0.2717	benign	-0.783	Destabilizing	0.994	D	0.529	neutral	N	0.492836034	None	None	N
E/C	0.9209	likely_pathogenic	0.9276	pathogenic	-0.239	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
E/D	0.322	likely_benign	0.3599	ambiguous	-0.889	Destabilizing	0.998	D	0.473	neutral	D	0.535387773	None	None	N
E/F	0.8206	likely_pathogenic	0.83	pathogenic	-0.493	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
E/G	0.3474	ambiguous	0.3683	ambiguous	-1.083	Destabilizing	0.999	D	0.673	neutral	N	0.519209176	None	None	N
E/H	0.6484	likely_pathogenic	0.6454	pathogenic	-0.653	Destabilizing	1.0	D	0.658	neutral	None	None	None	None	N
E/I	0.4985	ambiguous	0.5134	ambiguous	0.013	Stabilizing	0.784	D	0.525	neutral	None	None	None	None	N
E/K	0.3468	ambiguous	0.3504	ambiguous	-0.143	Destabilizing	0.998	D	0.517	neutral	D	0.527421651	None	None	N
E/L	0.5159	ambiguous	0.5677	pathogenic	0.013	Stabilizing	0.983	D	0.591	neutral	None	None	None	None	N
E/M	0.5877	likely_pathogenic	0.6027	pathogenic	0.414	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
E/N	0.5049	ambiguous	0.5147	ambiguous	-0.582	Destabilizing	1.0	D	0.654	neutral	None	None	None	None	N
E/P	0.9194	likely_pathogenic	0.9517	pathogenic	-0.231	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
E/Q	0.1758	likely_benign	0.1734	benign	-0.515	Destabilizing	0.999	D	0.629	neutral	N	0.492482358	None	None	N
E/R	0.4624	ambiguous	0.4487	ambiguous	0.04	Stabilizing	1.0	D	0.654	neutral	None	None	None	None	N
E/S	0.3252	likely_benign	0.3323	benign	-0.82	Destabilizing	0.999	D	0.551	neutral	None	None	None	None	N
E/T	0.3331	likely_benign	0.3399	benign	-0.569	Destabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	N
E/V	0.3091	likely_benign	0.3258	benign	-0.231	Destabilizing	0.978	D	0.554	neutral	N	0.490660442	None	None	N
E/W	0.9326	likely_pathogenic	0.9376	pathogenic	-0.26	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
E/Y	0.7408	likely_pathogenic	0.744	pathogenic	-0.225	Destabilizing	1.0	D	0.745	deleterious	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.