TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8517	25774;25775;25776	chr2:178717185;178717184;178717183	chr2:179581912;179581911;179581910
N2AB	8200	24823;24824;24825	chr2:178717185;178717184;178717183	chr2:179581912;179581911;179581910
N2A	7273	22042;22043;22044	chr2:178717185;178717184;178717183	chr2:179581912;179581911;179581910
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-70
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.8615
• 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/E	None	None	0.357	N	0.463	0.093	0.159798565429	gnomAD-4.0.0	1.59173E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85917E-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	0.7314	likely_pathogenic	0.7197	pathogenic	-0.068	Destabilizing	0.032	N	0.263	neutral	None	None	None	None	N
K/C	0.9248	likely_pathogenic	0.9274	pathogenic	-0.185	Destabilizing	0.995	D	0.413	neutral	None	None	None	None	N
K/D	0.8142	likely_pathogenic	0.7797	pathogenic	0.208	Stabilizing	0.946	D	0.402	neutral	None	None	None	None	N
K/E	0.5916	likely_pathogenic	0.5834	pathogenic	0.214	Stabilizing	0.357	N	0.463	neutral	N	0.454322962	None	None	N
K/F	0.9483	likely_pathogenic	0.946	pathogenic	-0.297	Destabilizing	0.874	D	0.414	neutral	None	None	None	None	N
K/G	0.7626	likely_pathogenic	0.7217	pathogenic	-0.277	Destabilizing	0.71	D	0.471	neutral	None	None	None	None	N
K/H	0.4104	ambiguous	0.4034	ambiguous	-0.608	Destabilizing	0.965	D	0.383	neutral	None	None	None	None	N
K/I	0.8359	likely_pathogenic	0.8506	pathogenic	0.401	Stabilizing	0.026	N	0.44	neutral	N	0.475165949	None	None	N
K/L	0.7327	likely_pathogenic	0.7315	pathogenic	0.401	Stabilizing	0.035	N	0.439	neutral	None	None	None	None	N
K/M	0.6055	likely_pathogenic	0.612	pathogenic	0.34	Stabilizing	0.675	D	0.387	neutral	None	None	None	None	N
K/N	0.6422	likely_pathogenic	0.601	pathogenic	0.279	Stabilizing	0.866	D	0.379	neutral	N	0.411606761	None	None	N
K/P	0.9496	likely_pathogenic	0.9376	pathogenic	0.273	Stabilizing	0.946	D	0.411	neutral	None	None	None	None	N
K/Q	0.2877	likely_benign	0.2976	benign	0.057	Stabilizing	0.439	N	0.428	neutral	N	0.488224892	None	None	N
K/R	0.0965	likely_benign	0.1032	benign	0.025	Stabilizing	0.002	N	0.357	neutral	N	0.42808051	None	None	N
K/S	0.736	likely_pathogenic	0.7195	pathogenic	-0.292	Destabilizing	0.55	D	0.393	neutral	None	None	None	None	N
K/T	0.5207	ambiguous	0.5358	ambiguous	-0.131	Destabilizing	0.007	N	0.289	neutral	N	0.473044796	None	None	N
K/V	0.7795	likely_pathogenic	0.7973	pathogenic	0.273	Stabilizing	0.001	N	0.291	neutral	None	None	None	None	N
K/W	0.9153	likely_pathogenic	0.9173	pathogenic	-0.259	Destabilizing	0.997	D	0.527	neutral	None	None	None	None	N
K/Y	0.8487	likely_pathogenic	0.8422	pathogenic	0.102	Stabilizing	0.712	D	0.418	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.