TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9069	27430;27431;27432	chr2:178712820;178712819;178712818	chr2:179577547;179577546;179577545
N2AB	8752	26479;26480;26481	chr2:178712820;178712819;178712818	chr2:179577547;179577546;179577545
N2A	7825	23698;23699;23700	chr2:178712820;178712819;178712818	chr2:179577547;179577546;179577545
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: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-76
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.5873
• 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
L/V	None	None	0.061	N	0.271	0.087	0.253726318573	gnomAD-4.0.0	1.59135E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41196E-04	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
L/A	0.2883	likely_benign	0.3463	ambiguous	-1.197	Destabilizing	0.863	D	0.557	neutral	None	None	None	None	N
L/C	0.5109	ambiguous	0.5575	ambiguous	-0.859	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	N
L/D	0.778	likely_pathogenic	0.8284	pathogenic	-0.311	Destabilizing	0.997	D	0.731	prob.delet.	None	None	None	None	N
L/E	0.4149	ambiguous	0.4978	ambiguous	-0.34	Destabilizing	0.997	D	0.732	prob.delet.	None	None	None	None	N
L/F	0.1035	likely_benign	0.0967	benign	-0.894	Destabilizing	0.077	N	0.274	neutral	N	0.492268927	None	None	N
L/G	0.592	likely_pathogenic	0.6779	pathogenic	-1.464	Destabilizing	0.997	D	0.709	prob.delet.	None	None	None	None	N
L/H	0.2454	likely_benign	0.2917	benign	-0.783	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
L/I	0.1029	likely_benign	0.1066	benign	-0.569	Destabilizing	0.17	N	0.243	neutral	None	None	None	None	N
L/K	0.2897	likely_benign	0.3741	ambiguous	-0.717	Destabilizing	0.997	D	0.734	prob.delet.	None	None	None	None	N
L/M	0.1064	likely_benign	0.1092	benign	-0.518	Destabilizing	0.988	D	0.631	neutral	N	0.511051967	None	None	N
L/N	0.5319	ambiguous	0.5896	pathogenic	-0.521	Destabilizing	0.997	D	0.729	prob.delet.	None	None	None	None	N
L/P	0.6336	likely_pathogenic	0.7418	pathogenic	-0.745	Destabilizing	0.997	D	0.729	prob.delet.	None	None	None	None	N
L/Q	0.1863	likely_benign	0.2363	benign	-0.689	Destabilizing	0.997	D	0.729	prob.delet.	None	None	None	None	N
L/R	0.1984	likely_benign	0.2679	benign	-0.239	Destabilizing	0.997	D	0.73	prob.delet.	None	None	None	None	N
L/S	0.3216	likely_benign	0.3836	ambiguous	-1.127	Destabilizing	0.988	D	0.697	prob.neutral	N	0.520839608	None	None	N
L/T	0.2427	likely_benign	0.2802	benign	-1.04	Destabilizing	0.939	D	0.615	neutral	None	None	None	None	N
L/V	0.0981	likely_benign	0.1024	benign	-0.745	Destabilizing	0.061	N	0.271	neutral	N	0.509025104	None	None	N
L/W	0.1712	likely_benign	0.199	benign	-0.933	Destabilizing	0.999	D	0.719	prob.delet.	D	0.522661762	None	None	N
L/Y	0.3387	likely_benign	0.3545	ambiguous	-0.683	Destabilizing	0.964	D	0.659	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.