TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30497	91714;91715;91716	chr2:178551042;178551041;178551040	chr2:179415769;179415768;179415767
N2AB	28856	86791;86792;86793	chr2:178551042;178551041;178551040	chr2:179415769;179415768;179415767
N2A	27929	84010;84011;84012	chr2:178551042;178551041;178551040	chr2:179415769;179415768;179415767
N2B	21432	64519;64520;64521	chr2:178551042;178551041;178551040	chr2:179415769;179415768;179415767
Novex-1	21557	64894;64895;64896	chr2:178551042;178551041;178551040	chr2:179415769;179415768;179415767
Novex-2	21624	65095;65096;65097	chr2:178551042;178551041;178551040	chr2:179415769;179415768;179415767
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-110
• Domain position: 76
• Structural Position: 109
• Q(SASA): 0.1051
• 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
I/V	None	None	0.19	N	0.42	0.05	0.519133540473	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	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
I/A	0.4335	ambiguous	0.43	ambiguous	-2.255	Highly Destabilizing	0.775	D	0.737	prob.delet.	None	None	None	None	N
I/C	0.7385	likely_pathogenic	0.7559	pathogenic	-1.738	Destabilizing	0.996	D	0.74	deleterious	None	None	None	None	N
I/D	0.9701	likely_pathogenic	0.9729	pathogenic	-2.018	Highly Destabilizing	0.987	D	0.817	deleterious	None	None	None	None	N
I/E	0.9009	likely_pathogenic	0.9056	pathogenic	-1.92	Destabilizing	0.961	D	0.804	deleterious	None	None	None	None	N
I/F	0.1957	likely_benign	0.2044	benign	-1.459	Destabilizing	0.82	D	0.773	deleterious	N	0.496970166	None	None	N
I/G	0.8609	likely_pathogenic	0.8668	pathogenic	-2.674	Highly Destabilizing	0.961	D	0.788	deleterious	None	None	None	None	N
I/H	0.6975	likely_pathogenic	0.7074	pathogenic	-1.876	Destabilizing	0.996	D	0.783	deleterious	None	None	None	None	N
I/K	0.6514	likely_pathogenic	0.6635	pathogenic	-1.534	Destabilizing	0.961	D	0.783	deleterious	None	None	None	None	N
I/L	0.1166	likely_benign	0.1169	benign	-1.11	Destabilizing	0.003	N	0.249	neutral	N	0.485502379	None	None	N
I/M	0.1059	likely_benign	0.1105	benign	-1.111	Destabilizing	0.19	N	0.523	neutral	N	0.467431992	None	None	N
I/N	0.6593	likely_pathogenic	0.6836	pathogenic	-1.54	Destabilizing	0.983	D	0.809	deleterious	N	0.497195267	None	None	N
I/P	0.9864	likely_pathogenic	0.989	pathogenic	-1.467	Destabilizing	0.987	D	0.812	deleterious	None	None	None	None	N
I/Q	0.6816	likely_pathogenic	0.6938	pathogenic	-1.631	Destabilizing	0.961	D	0.815	deleterious	None	None	None	None	N
I/R	0.5005	ambiguous	0.524	ambiguous	-1.064	Destabilizing	0.961	D	0.817	deleterious	None	None	None	None	N
I/S	0.4756	ambiguous	0.4821	ambiguous	-2.268	Highly Destabilizing	0.949	D	0.751	deleterious	N	0.452813957	None	None	N
I/T	0.1976	likely_benign	0.1857	benign	-2.043	Highly Destabilizing	0.722	D	0.755	deleterious	N	0.491985634	None	None	N
I/V	0.1011	likely_benign	0.1005	benign	-1.467	Destabilizing	0.19	N	0.42	neutral	N	0.459566571	None	None	N
I/W	0.8128	likely_pathogenic	0.8286	pathogenic	-1.596	Destabilizing	0.996	D	0.785	deleterious	None	None	None	None	N
I/Y	0.6343	likely_pathogenic	0.6619	pathogenic	-1.368	Destabilizing	0.961	D	0.783	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.