TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9192	27799;27800;27801	chr2:178712348;178712347;178712346	chr2:179577075;179577074;179577073
N2AB	8875	26848;26849;26850	chr2:178712348;178712347;178712346	chr2:179577075;179577074;179577073
N2A	7948	24067;24068;24069	chr2:178712348;178712347;178712346	chr2:179577075;179577074;179577073
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-77
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.6568
• 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
K/R	None	None	0.001	N	0.229	0.083	0.230578612272	gnomAD-4.0.0	4.7742E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.5754E-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
K/A	0.2228	likely_benign	0.2388	benign	0.001	Stabilizing	0.388	N	0.459	neutral	None	None	None	None	I
K/C	0.6141	likely_pathogenic	0.6079	pathogenic	-0.155	Destabilizing	0.981	D	0.578	neutral	None	None	None	None	I
K/D	0.4532	ambiguous	0.4865	ambiguous	0.045	Stabilizing	0.241	N	0.529	neutral	None	None	None	None	I
K/E	0.096	likely_benign	0.112	benign	0.046	Stabilizing	0.09	N	0.408	neutral	N	0.472144371	None	None	I
K/F	0.567	likely_pathogenic	0.5942	pathogenic	-0.215	Destabilizing	0.818	D	0.54	neutral	None	None	None	None	I
K/G	0.3188	likely_benign	0.3282	benign	-0.2	Destabilizing	0.388	N	0.535	neutral	None	None	None	None	I
K/H	0.2427	likely_benign	0.2616	benign	-0.501	Destabilizing	0.005	N	0.405	neutral	None	None	None	None	I
K/I	0.2455	likely_benign	0.2644	benign	0.45	Stabilizing	0.773	D	0.539	neutral	N	0.520575823	None	None	I
K/L	0.2749	likely_benign	0.2888	benign	0.45	Stabilizing	0.388	N	0.55	neutral	None	None	None	None	I
K/M	0.1441	likely_benign	0.1576	benign	0.313	Stabilizing	0.944	D	0.515	neutral	None	None	None	None	I
K/N	0.2637	likely_benign	0.2891	benign	0.296	Stabilizing	0.006	N	0.261	neutral	N	0.48244151	None	None	I
K/P	0.8508	likely_pathogenic	0.8255	pathogenic	0.329	Stabilizing	0.818	D	0.518	neutral	None	None	None	None	I
K/Q	0.0906	likely_benign	0.099	benign	0.074	Stabilizing	0.015	N	0.256	neutral	N	0.462834242	None	None	I
K/R	0.0748	likely_benign	0.0751	benign	0.028	Stabilizing	0.001	N	0.229	neutral	N	0.453004037	None	None	I
K/S	0.229	likely_benign	0.2536	benign	-0.209	Destabilizing	0.388	N	0.405	neutral	None	None	None	None	I
K/T	0.1054	likely_benign	0.1169	benign	-0.062	Destabilizing	0.324	N	0.531	neutral	N	0.444211195	None	None	I
K/V	0.2334	likely_benign	0.2503	benign	0.329	Stabilizing	0.69	D	0.527	neutral	None	None	None	None	I
K/W	0.618	likely_pathogenic	0.6121	pathogenic	-0.201	Destabilizing	0.981	D	0.613	neutral	None	None	None	None	I
K/Y	0.4686	ambiguous	0.4885	ambiguous	0.155	Stabilizing	0.69	D	0.55	neutral	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.