TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29068	87427;87428;87429	chr2:178558152;178558151;178558150	chr2:179422879;179422878;179422877
N2AB	27427	82504;82505;82506	chr2:178558152;178558151;178558150	chr2:179422879;179422878;179422877
N2A	26500	79723;79724;79725	chr2:178558152;178558151;178558150	chr2:179422879;179422878;179422877
N2B	20003	60232;60233;60234	chr2:178558152;178558151;178558150	chr2:179422879;179422878;179422877
Novex-1	20128	60607;60608;60609	chr2:178558152;178558151;178558150	chr2:179422879;179422878;179422877
Novex-2	20195	60808;60809;60810	chr2:178558152;178558151;178558150	chr2:179422879;179422878;179422877
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-145
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.105
• 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
I/V	rs766759385	-1.675	0.005	N	0.205	0.067	0.288352970974	gnomAD-2.1.1	1.24939E-04	None	None	None	None	N	None	0	0	None	0	0	None	9.80777E-04	None	0	0	1.66334E-04
I/V	rs766759385	-1.675	0.005	N	0.205	0.067	0.288352970974	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.06954E-04	0
I/V	rs766759385	-1.675	0.005	N	0.205	0.067	0.288352970974	gnomAD-4.0.0	5.0814E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	1.64528E-04	5.933E-06	7.79483E-04	4.80292E-05

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
I/A	0.7851	likely_pathogenic	0.7314	pathogenic	-1.913	Destabilizing	0.525	D	0.655	neutral	None	None	None	None	N
I/C	0.8347	likely_pathogenic	0.8049	pathogenic	-1.367	Destabilizing	0.998	D	0.725	prob.delet.	None	None	None	None	N
I/D	0.9966	likely_pathogenic	0.9945	pathogenic	-1.234	Destabilizing	0.991	D	0.82	deleterious	None	None	None	None	N
I/E	0.9899	likely_pathogenic	0.984	pathogenic	-1.2	Destabilizing	0.974	D	0.815	deleterious	None	None	None	None	N
I/F	0.2209	likely_benign	0.1893	benign	-1.33	Destabilizing	0.934	D	0.724	prob.delet.	N	0.472341946	None	None	N
I/G	0.968	likely_pathogenic	0.951	pathogenic	-2.279	Highly Destabilizing	0.974	D	0.803	deleterious	None	None	None	None	N
I/H	0.9534	likely_pathogenic	0.9362	pathogenic	-1.472	Destabilizing	0.998	D	0.775	deleterious	None	None	None	None	N
I/K	0.9673	likely_pathogenic	0.9549	pathogenic	-1.396	Destabilizing	0.974	D	0.804	deleterious	None	None	None	None	N
I/L	0.1296	likely_benign	0.1176	benign	-0.962	Destabilizing	0.002	N	0.227	neutral	N	0.455313623	None	None	N
I/M	0.205	likely_benign	0.1825	benign	-0.803	Destabilizing	0.934	D	0.689	prob.neutral	N	0.494765499	None	None	N
I/N	0.9567	likely_pathogenic	0.9374	pathogenic	-1.263	Destabilizing	0.989	D	0.817	deleterious	N	0.495272478	None	None	N
I/P	0.9883	likely_pathogenic	0.9827	pathogenic	-1.248	Destabilizing	0.991	D	0.817	deleterious	None	None	None	None	N
I/Q	0.9665	likely_pathogenic	0.9518	pathogenic	-1.393	Destabilizing	0.991	D	0.809	deleterious	None	None	None	None	N
I/R	0.942	likely_pathogenic	0.9225	pathogenic	-0.824	Destabilizing	0.974	D	0.817	deleterious	None	None	None	None	N
I/S	0.9088	likely_pathogenic	0.871	pathogenic	-1.958	Destabilizing	0.891	D	0.783	deleterious	N	0.507166596	None	None	N
I/T	0.8329	likely_pathogenic	0.773	pathogenic	-1.795	Destabilizing	0.801	D	0.705	prob.neutral	N	0.493498052	None	None	N
I/V	0.064	likely_benign	0.0635	benign	-1.248	Destabilizing	0.005	N	0.205	neutral	N	0.444565407	None	None	N
I/W	0.9459	likely_pathogenic	0.9318	pathogenic	-1.401	Destabilizing	0.998	D	0.773	deleterious	None	None	None	None	N
I/Y	0.7806	likely_pathogenic	0.7302	pathogenic	-1.189	Destabilizing	0.974	D	0.77	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.