TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16670	50233;50234;50235	chr2:178612517;178612516;178612515	chr2:179477244;179477243;179477242
N2AB	15029	45310;45311;45312	chr2:178612517;178612516;178612515	chr2:179477244;179477243;179477242
N2A	14102	42529;42530;42531	chr2:178612517;178612516;178612515	chr2:179477244;179477243;179477242
N2B	7605	23038;23039;23040	chr2:178612517;178612516;178612515	chr2:179477244;179477243;179477242
Novex-1	7730	23413;23414;23415	chr2:178612517;178612516;178612515	chr2:179477244;179477243;179477242
Novex-2	7797	23614;23615;23616	chr2:178612517;178612516;178612515	chr2:179477244;179477243;179477242
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-9
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.1091
• 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/I	None	None	0.999	N	0.556	0.312	0.307332253619	gnomAD-4.0.0	1.59526E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4339E-05	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	0.9853	likely_pathogenic	0.9914	pathogenic	-2.714	Highly Destabilizing	0.999	D	0.724	prob.delet.	None	None	None	None	N
L/C	0.9743	likely_pathogenic	0.9783	pathogenic	-1.87	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9999	pathogenic	-3.459	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
L/E	0.9986	likely_pathogenic	0.9994	pathogenic	-3.133	Highly Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
L/F	0.8873	likely_pathogenic	0.9299	pathogenic	-1.636	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
L/G	0.9977	likely_pathogenic	0.9989	pathogenic	-3.337	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
L/H	0.9983	likely_pathogenic	0.9993	pathogenic	-3.08	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
L/I	0.2221	likely_benign	0.2494	benign	-0.844	Destabilizing	0.999	D	0.556	neutral	N	0.518014734	None	None	N
L/K	0.9974	likely_pathogenic	0.9989	pathogenic	-2.132	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
L/M	0.5464	ambiguous	0.595	pathogenic	-0.939	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
L/N	0.9989	likely_pathogenic	0.9996	pathogenic	-2.847	Highly Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	N
L/P	0.9993	likely_pathogenic	0.9998	pathogenic	-1.457	Destabilizing	1.0	D	0.915	deleterious	D	0.799569317	None	None	N
L/Q	0.9968	likely_pathogenic	0.9987	pathogenic	-2.487	Highly Destabilizing	1.0	D	0.909	deleterious	D	0.799569317	None	None	N
L/R	0.9953	likely_pathogenic	0.998	pathogenic	-2.175	Highly Destabilizing	1.0	D	0.895	deleterious	D	0.799569317	None	None	N
L/S	0.9988	likely_pathogenic	0.9995	pathogenic	-3.415	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
L/T	0.9881	likely_pathogenic	0.9941	pathogenic	-2.921	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
L/V	0.3491	ambiguous	0.3704	ambiguous	-1.457	Destabilizing	0.999	D	0.568	neutral	D	0.529888999	None	None	N
L/W	0.9953	likely_pathogenic	0.9982	pathogenic	-2.111	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
L/Y	0.9952	likely_pathogenic	0.9977	pathogenic	-1.847	Destabilizing	1.0	D	0.824	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.