TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20457	61594;61595;61596	chr2:178590356;178590355;178590354	chr2:179455083;179455082;179455081
N2AB	18816	56671;56672;56673	chr2:178590356;178590355;178590354	chr2:179455083;179455082;179455081
N2A	17889	53890;53891;53892	chr2:178590356;178590355;178590354	chr2:179455083;179455082;179455081
N2B	11392	34399;34400;34401	chr2:178590356;178590355;178590354	chr2:179455083;179455082;179455081
Novex-1	11517	34774;34775;34776	chr2:178590356;178590355;178590354	chr2:179455083;179455082;179455081
Novex-2	11584	34975;34976;34977	chr2:178590356;178590355;178590354	chr2:179455083;179455082;179455081
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-36
• Domain position: 87
• Structural Position: 119
• Q(SASA): 0.5488
• 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
E/A	rs541930965	-0.475	0.067	N	0.422	0.251	0.268660756437	gnomAD-2.1.1	3.69E-05	None	None	None	None	I	None	0	0	None	0	0	None	3.71747E-04	None	0	0	0
E/A	rs541930965	-0.475	0.067	N	0.422	0.251	0.268660756437	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	4.14594E-04	0
E/A	rs541930965	-0.475	0.067	N	0.422	0.251	0.268660756437	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	0	0	None	None	None	1E-03	None
E/A	rs541930965	-0.475	0.067	N	0.422	0.251	0.268660756437	gnomAD-4.0.0	1.3328E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.53961E-04	0
E/K	None	None	0.958	N	0.584	0.295	0.300110245524	gnomAD-4.0.0	2.10783E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.74246E-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
E/A	0.2544	likely_benign	0.2864	benign	-0.349	Destabilizing	0.067	N	0.422	neutral	N	0.472850042	None	None	I
E/C	0.9035	likely_pathogenic	0.9186	pathogenic	-0.143	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	I
E/D	0.1568	likely_benign	0.1595	benign	-0.351	Destabilizing	0.979	D	0.529	neutral	N	0.515884001	None	None	I
E/F	0.8371	likely_pathogenic	0.8413	pathogenic	-0.201	Destabilizing	0.995	D	0.724	prob.delet.	None	None	None	None	I
E/G	0.3702	ambiguous	0.3871	ambiguous	-0.55	Destabilizing	0.919	D	0.625	neutral	N	0.502626544	None	None	I
E/H	0.7223	likely_pathogenic	0.7321	pathogenic	0.097	Stabilizing	1.0	D	0.633	neutral	None	None	None	None	I
E/I	0.438	ambiguous	0.4679	ambiguous	0.145	Stabilizing	0.991	D	0.715	prob.delet.	None	None	None	None	I
E/K	0.3297	likely_benign	0.3278	benign	0.21	Stabilizing	0.958	D	0.584	neutral	N	0.497316883	None	None	I
E/L	0.49	ambiguous	0.5075	ambiguous	0.145	Stabilizing	0.982	D	0.648	neutral	None	None	None	None	I
E/M	0.54	ambiguous	0.5781	pathogenic	0.154	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
E/N	0.398	ambiguous	0.4043	ambiguous	-0.059	Destabilizing	0.995	D	0.679	prob.neutral	None	None	None	None	I
E/P	0.4801	ambiguous	0.5089	ambiguous	0.001	Stabilizing	0.995	D	0.695	prob.neutral	None	None	None	None	I
E/Q	0.2317	likely_benign	0.2487	benign	-0.025	Destabilizing	0.994	D	0.674	neutral	N	0.470141017	None	None	I
E/R	0.5234	ambiguous	0.5396	ambiguous	0.485	Stabilizing	0.995	D	0.677	prob.neutral	None	None	None	None	I
E/S	0.3422	ambiguous	0.3677	ambiguous	-0.249	Destabilizing	0.938	D	0.571	neutral	None	None	None	None	I
E/T	0.3936	ambiguous	0.4339	ambiguous	-0.087	Destabilizing	0.991	D	0.66	neutral	None	None	None	None	I
E/V	0.2904	likely_benign	0.3219	benign	0.001	Stabilizing	0.976	D	0.624	neutral	N	0.481777265	None	None	I
E/W	0.9517	likely_pathogenic	0.9547	pathogenic	-0.052	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
E/Y	0.7616	likely_pathogenic	0.7651	pathogenic	0.042	Stabilizing	0.998	D	0.715	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.