TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23641	71146;71147;71148	chr2:178575211;178575210;178575209	chr2:179439938;179439937;179439936
N2AB	22000	66223;66224;66225	chr2:178575211;178575210;178575209	chr2:179439938;179439937;179439936
N2A	21073	63442;63443;63444	chr2:178575211;178575210;178575209	chr2:179439938;179439937;179439936
N2B	14576	43951;43952;43953	chr2:178575211;178575210;178575209	chr2:179439938;179439937;179439936
Novex-1	14701	44326;44327;44328	chr2:178575211;178575210;178575209	chr2:179439938;179439937;179439936
Novex-2	14768	44527;44528;44529	chr2:178575211;178575210;178575209	chr2:179439938;179439937;179439936
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-130
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.4312
• 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
K/Q	rs778715011	-0.636	0.817	N	0.291	0.159	0.223847106136	gnomAD-2.1.1	1.22E-05	None	None	None	None	N	None	0	0	None	0	5.68E-05	None	6.57E-05	None	0	0	0
K/Q	rs778715011	-0.636	0.817	N	0.291	0.159	0.223847106136	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07039E-04	0
K/Q	rs778715011	-0.636	0.817	N	0.291	0.159	0.223847106136	gnomAD-4.0.0	8.06037E-06	None	None	None	None	N	None	0	0	None	0	2.24235E-05	None	0	0	2.5435E-06	9.89381E-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
K/A	0.7307	likely_pathogenic	0.8033	pathogenic	-0.101	Destabilizing	0.985	D	0.557	neutral	None	None	None	None	N
K/C	0.8204	likely_pathogenic	0.8491	pathogenic	-0.274	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
K/D	0.7037	likely_pathogenic	0.78	pathogenic	0.203	Stabilizing	0.971	D	0.601	neutral	None	None	None	None	N
K/E	0.4336	ambiguous	0.5243	ambiguous	0.264	Stabilizing	0.961	D	0.552	neutral	N	0.510099753	None	None	N
K/F	0.9455	likely_pathogenic	0.9622	pathogenic	-0.036	Destabilizing	0.998	D	0.718	prob.delet.	None	None	None	None	N
K/G	0.5284	ambiguous	0.5968	pathogenic	-0.389	Destabilizing	0.985	D	0.625	neutral	None	None	None	None	N
K/H	0.3626	ambiguous	0.4178	ambiguous	-0.747	Destabilizing	0.998	D	0.667	neutral	None	None	None	None	N
K/I	0.8881	likely_pathogenic	0.9216	pathogenic	0.604	Stabilizing	0.989	D	0.716	prob.delet.	N	0.494905814	None	None	N
K/L	0.7072	likely_pathogenic	0.7747	pathogenic	0.604	Stabilizing	0.971	D	0.588	neutral	None	None	None	None	N
K/M	0.5422	ambiguous	0.6276	pathogenic	0.293	Stabilizing	0.931	D	0.475	neutral	None	None	None	None	N
K/N	0.4752	ambiguous	0.5551	ambiguous	-0.009	Destabilizing	0.606	D	0.286	neutral	N	0.499845474	None	None	N
K/P	0.8985	likely_pathogenic	0.9284	pathogenic	0.4	Stabilizing	0.999	D	0.671	neutral	None	None	None	None	N
K/Q	0.2104	likely_benign	0.2604	benign	-0.079	Destabilizing	0.817	D	0.291	neutral	N	0.474525742	None	None	N
K/R	0.1196	likely_benign	0.1298	benign	-0.318	Destabilizing	0.98	D	0.511	neutral	N	0.470042642	None	None	N
K/S	0.6421	likely_pathogenic	0.7241	pathogenic	-0.543	Destabilizing	0.985	D	0.522	neutral	None	None	None	None	N
K/T	0.5198	ambiguous	0.6207	pathogenic	-0.301	Destabilizing	0.98	D	0.603	neutral	N	0.503251138	None	None	N
K/V	0.8342	likely_pathogenic	0.8842	pathogenic	0.4	Stabilizing	0.971	D	0.633	neutral	None	None	None	None	N
K/W	0.9155	likely_pathogenic	0.9374	pathogenic	-0.019	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
K/Y	0.7761	likely_pathogenic	0.8241	pathogenic	0.309	Stabilizing	0.999	D	0.704	prob.neutral	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.