TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1924	5995;5996;5997	chr2:178776094;178776093;178776092	chr2:179640821;179640820;179640819
N2AB	1924	5995;5996;5997	chr2:178776094;178776093;178776092	chr2:179640821;179640820;179640819
N2A	1924	5995;5996;5997	chr2:178776094;178776093;178776092	chr2:179640821;179640820;179640819
N2B	1878	5857;5858;5859	chr2:178776094;178776093;178776092	chr2:179640821;179640820;179640819
Novex-1	1878	5857;5858;5859	chr2:178776094;178776093;178776092	chr2:179640821;179640820;179640819
Novex-2	1878	5857;5858;5859	chr2:178776094;178776093;178776092	chr2:179640821;179640820;179640819
Novex-3	1924	5995;5996;5997	chr2:178776094;178776093;178776092	chr2:179640821;179640820;179640819

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-9
• Domain position: 84
• Structural Position: 171
• Q(SASA): 0.5068
• 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/E	rs1327562179	0.204	0.183	N	0.411	0.318	0.26169431596	gnomAD-2.1.1	7.96E-06	None	None	None	None	I	None	0	5.78E-05	None	0	0	None	0	None	0	0	0
K/E	rs1327562179	0.204	0.183	N	0.411	0.318	0.26169431596	gnomAD-4.0.0	3.42034E-06	None	None	None	None	I	None	0	4.47207E-05	None	0	0	None	0	0	8.993E-07	2.31863E-05	0
K/N	None	None	0.351	N	0.425	0.127	0.218112801441	gnomAD-4.0.0	1.5905E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85656E-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	0.3543	ambiguous	0.452	ambiguous	-0.308	Destabilizing	0.061	N	0.311	neutral	None	None	None	None	I
K/C	0.6473	likely_pathogenic	0.6901	pathogenic	-0.29	Destabilizing	0.94	D	0.552	neutral	None	None	None	None	I
K/D	0.7732	likely_pathogenic	0.8412	pathogenic	-0.264	Destabilizing	0.418	N	0.537	neutral	None	None	None	None	I
K/E	0.2971	likely_benign	0.3979	ambiguous	-0.174	Destabilizing	0.183	N	0.411	neutral	N	0.482690385	None	None	I
K/F	0.8719	likely_pathogenic	0.9023	pathogenic	0.049	Stabilizing	0.716	D	0.627	neutral	None	None	None	None	I
K/G	0.6119	likely_pathogenic	0.7037	pathogenic	-0.658	Destabilizing	0.228	N	0.474	neutral	None	None	None	None	I
K/H	0.3257	likely_benign	0.3665	ambiguous	-1.044	Destabilizing	0.836	D	0.567	neutral	None	None	None	None	I
K/I	0.3854	ambiguous	0.4669	ambiguous	0.589	Stabilizing	0.001	N	0.357	neutral	N	0.503037484	None	None	I
K/L	0.4464	ambiguous	0.5323	ambiguous	0.589	Stabilizing	0.061	N	0.375	neutral	None	None	None	None	I
K/M	0.2774	likely_benign	0.351	ambiguous	0.336	Stabilizing	0.716	D	0.569	neutral	None	None	None	None	I
K/N	0.5546	ambiguous	0.6417	pathogenic	-0.345	Destabilizing	0.351	N	0.425	neutral	N	0.468624494	None	None	I
K/P	0.8423	likely_pathogenic	0.8985	pathogenic	0.32	Stabilizing	0.593	D	0.595	neutral	None	None	None	None	I
K/Q	0.1584	likely_benign	0.1882	benign	-0.385	Destabilizing	0.351	N	0.497	neutral	N	0.495891639	None	None	I
K/R	0.093	likely_benign	0.0956	benign	-0.681	Destabilizing	0.002	N	0.151	neutral	N	0.493907906	None	None	I
K/S	0.4491	ambiguous	0.5438	ambiguous	-0.82	Destabilizing	0.129	N	0.355	neutral	None	None	None	None	I
K/T	0.1262	likely_benign	0.1706	benign	-0.547	Destabilizing	0.001	N	0.227	neutral	N	0.395664044	None	None	I
K/V	0.3071	likely_benign	0.3727	ambiguous	0.32	Stabilizing	0.001	N	0.29	neutral	None	None	None	None	I
K/W	0.8527	likely_pathogenic	0.881	pathogenic	0.087	Stabilizing	0.983	D	0.561	neutral	None	None	None	None	I
K/Y	0.7763	likely_pathogenic	0.8169	pathogenic	0.345	Stabilizing	0.94	D	0.607	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.