TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22113	66562;66563;66564	chr2:178582032;178582031;178582030	chr2:179446759;179446758;179446757
N2AB	20472	61639;61640;61641	chr2:178582032;178582031;178582030	chr2:179446759;179446758;179446757
N2A	19545	58858;58859;58860	chr2:178582032;178582031;178582030	chr2:179446759;179446758;179446757
N2B	13048	39367;39368;39369	chr2:178582032;178582031;178582030	chr2:179446759;179446758;179446757
Novex-1	13173	39742;39743;39744	chr2:178582032;178582031;178582030	chr2:179446759;179446758;179446757
Novex-2	13240	39943;39944;39945	chr2:178582032;178582031;178582030	chr2:179446759;179446758;179446757
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-48
• Domain position: 59
• Structural Position: 89
• Q(SASA): 0.596
• 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
R/K	rs748719400	-0.37	0.997	N	0.552	0.258	0.233785782151	gnomAD-4.0.0	1.59217E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86044E-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
R/A	0.8556	likely_pathogenic	0.7622	pathogenic	-1.133	Destabilizing	0.999	D	0.616	neutral	None	None	None	None	I
R/C	0.4557	ambiguous	0.3055	benign	-1.228	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
R/D	0.9333	likely_pathogenic	0.8851	pathogenic	-0.68	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	I
R/E	0.7964	likely_pathogenic	0.6784	pathogenic	-0.476	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	I
R/F	0.9514	likely_pathogenic	0.9039	pathogenic	-0.575	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
R/G	0.7107	likely_pathogenic	0.5659	pathogenic	-1.481	Destabilizing	1.0	D	0.657	neutral	N	0.482961672	None	None	I
R/H	0.4043	ambiguous	0.2647	benign	-1.512	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	I
R/I	0.8199	likely_pathogenic	0.6838	pathogenic	-0.158	Destabilizing	1.0	D	0.727	prob.delet.	N	0.470844898	None	None	I
R/K	0.2637	likely_benign	0.1996	benign	-0.804	Destabilizing	0.997	D	0.552	neutral	N	0.496255303	None	None	I
R/L	0.6266	likely_pathogenic	0.4805	ambiguous	-0.158	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	I
R/M	0.7322	likely_pathogenic	0.5773	pathogenic	-0.764	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
R/N	0.853	likely_pathogenic	0.7718	pathogenic	-0.995	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
R/P	0.8374	likely_pathogenic	0.719	pathogenic	-0.466	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	I
R/Q	0.3254	likely_benign	0.2115	benign	-0.883	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
R/S	0.9159	likely_pathogenic	0.8468	pathogenic	-1.651	Destabilizing	1.0	D	0.72	prob.delet.	N	0.507317659	None	None	I
R/T	0.6731	likely_pathogenic	0.502	ambiguous	-1.233	Destabilizing	1.0	D	0.717	prob.delet.	N	0.422445404	None	None	I
R/V	0.8166	likely_pathogenic	0.6998	pathogenic	-0.466	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	I
R/W	0.6896	likely_pathogenic	0.5025	ambiguous	-0.255	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
R/Y	0.8205	likely_pathogenic	0.6898	pathogenic	-0.057	Destabilizing	1.0	D	0.729	prob.delet.	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.