TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14579	43960;43961;43962	chr2:178632159;178632158;178632157	chr2:179496886;179496885;179496884
N2AB	12938	39037;39038;39039	chr2:178632159;178632158;178632157	chr2:179496886;179496885;179496884
N2A	12011	36256;36257;36258	chr2:178632159;178632158;178632157	chr2:179496886;179496885;179496884
N2B	5514	16765;16766;16767	chr2:178632159;178632158;178632157	chr2:179496886;179496885;179496884
Novex-1	5639	17140;17141;17142	chr2:178632159;178632158;178632157	chr2:179496886;179496885;179496884
Novex-2	5706	17341;17342;17343	chr2:178632159;178632158;178632157	chr2:179496886;179496885;179496884
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-96
• Domain position: 83
• Structural Position: 174
• Q(SASA): 0.1037
• 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/P	None	None	1.0	D	0.801	0.866	0.925466202161	gnomAD-4.0.0	6.91713E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.05754E-07	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	0.9559	likely_pathogenic	0.9566	pathogenic	-3.057	Highly Destabilizing	0.999	D	0.659	neutral	None	None	None	None	N
L/C	0.9488	likely_pathogenic	0.9518	pathogenic	-2.541	Highly Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
L/D	0.9987	likely_pathogenic	0.999	pathogenic	-3.702	Highly Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
L/E	0.9918	likely_pathogenic	0.9935	pathogenic	-3.394	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
L/F	0.7508	likely_pathogenic	0.7853	pathogenic	-1.757	Destabilizing	1.0	D	0.733	prob.delet.	D	0.725847472	None	None	N
L/G	0.9868	likely_pathogenic	0.9889	pathogenic	-3.663	Highly Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
L/H	0.9847	likely_pathogenic	0.9894	pathogenic	-3.216	Highly Destabilizing	1.0	D	0.787	deleterious	D	0.725847472	None	None	N
L/I	0.2951	likely_benign	0.3338	benign	-1.236	Destabilizing	0.999	D	0.529	neutral	D	0.727544819	None	None	N
L/K	0.9834	likely_pathogenic	0.9893	pathogenic	-2.322	Highly Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
L/M	0.3927	ambiguous	0.4133	ambiguous	-1.53	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
L/N	0.9925	likely_pathogenic	0.9941	pathogenic	-2.982	Highly Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
L/P	0.9952	likely_pathogenic	0.9962	pathogenic	-1.834	Destabilizing	1.0	D	0.801	deleterious	D	0.725755222	None	None	N
L/Q	0.9756	likely_pathogenic	0.982	pathogenic	-2.671	Highly Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
L/R	0.9724	likely_pathogenic	0.9798	pathogenic	-2.239	Highly Destabilizing	1.0	D	0.801	deleterious	D	0.726895652	None	None	N
L/S	0.9935	likely_pathogenic	0.9949	pathogenic	-3.603	Highly Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
L/T	0.9742	likely_pathogenic	0.9798	pathogenic	-3.133	Highly Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
L/V	0.3911	ambiguous	0.4345	ambiguous	-1.834	Destabilizing	0.999	D	0.533	neutral	D	0.629612073	None	None	N
L/W	0.9564	likely_pathogenic	0.9718	pathogenic	-2.165	Highly Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
L/Y	0.9581	likely_pathogenic	0.9704	pathogenic	-2.006	Highly Destabilizing	1.0	D	0.795	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.