TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8491	25696;25697;25698	chr2:178717263;178717262;178717261	chr2:179581990;179581989;179581988
N2AB	8174	24745;24746;24747	chr2:178717263;178717262;178717261	chr2:179581990;179581989;179581988
N2A	7247	21964;21965;21966	chr2:178717263;178717262;178717261	chr2:179581990;179581989;179581988
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: 36
• Structural Position: 50
• Q(SASA): 0.1918
• 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/R	None	None	0.04	N	0.275	0.158	0.253726318573	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.9752	likely_pathogenic	0.9699	pathogenic	-1.158	Destabilizing	0.99	D	0.512	neutral	None	None	None	None	N
K/C	0.9816	likely_pathogenic	0.9756	pathogenic	-1.211	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
K/D	0.9975	likely_pathogenic	0.9972	pathogenic	-0.972	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
K/E	0.9532	likely_pathogenic	0.9444	pathogenic	-0.75	Destabilizing	0.956	D	0.469	neutral	D	0.541793887	None	None	N
K/F	0.9894	likely_pathogenic	0.9884	pathogenic	-0.698	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
K/G	0.9875	likely_pathogenic	0.9846	pathogenic	-1.616	Destabilizing	0.999	D	0.72	prob.delet.	None	None	None	None	N
K/H	0.833	likely_pathogenic	0.8385	pathogenic	-1.927	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
K/I	0.9648	likely_pathogenic	0.9551	pathogenic	0.094	Stabilizing	0.938	D	0.849	deleterious	N	0.511065879	None	None	N
K/L	0.9342	likely_pathogenic	0.9111	pathogenic	0.094	Stabilizing	0.908	D	0.72	prob.delet.	None	None	None	None	N
K/M	0.8991	likely_pathogenic	0.8753	pathogenic	-0.051	Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
K/N	0.9891	likely_pathogenic	0.9867	pathogenic	-1.265	Destabilizing	0.996	D	0.651	neutral	N	0.515042352	None	None	N
K/P	0.9985	likely_pathogenic	0.9979	pathogenic	-0.297	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
K/Q	0.7637	likely_pathogenic	0.7236	pathogenic	-1.11	Destabilizing	0.969	D	0.637	neutral	D	0.522929164	None	None	N
K/R	0.1114	likely_benign	0.1044	benign	-0.949	Destabilizing	0.04	N	0.275	neutral	N	0.458293143	None	None	N
K/S	0.988	likely_pathogenic	0.9855	pathogenic	-1.932	Destabilizing	0.99	D	0.552	neutral	None	None	None	None	N
K/T	0.9723	likely_pathogenic	0.964	pathogenic	-1.455	Destabilizing	0.994	D	0.711	prob.delet.	N	0.500305458	None	None	N
K/V	0.9316	likely_pathogenic	0.9197	pathogenic	-0.297	Destabilizing	0.964	D	0.789	deleterious	None	None	None	None	N
K/W	0.9793	likely_pathogenic	0.9778	pathogenic	-0.636	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
K/Y	0.9713	likely_pathogenic	0.9703	pathogenic	-0.291	Destabilizing	0.99	D	0.831	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.