TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22324	67195;67196;67197	chr2:178580409;178580408;178580407	chr2:179445136;179445135;179445134
N2AB	20683	62272;62273;62274	chr2:178580409;178580408;178580407	chr2:179445136;179445135;179445134
N2A	19756	59491;59492;59493	chr2:178580409;178580408;178580407	chr2:179445136;179445135;179445134
N2B	13259	40000;40001;40002	chr2:178580409;178580408;178580407	chr2:179445136;179445135;179445134
Novex-1	13384	40375;40376;40377	chr2:178580409;178580408;178580407	chr2:179445136;179445135;179445134
Novex-2	13451	40576;40577;40578	chr2:178580409;178580408;178580407	chr2:179445136;179445135;179445134
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-126
• Domain position: 60
• Structural Position: 144
• Q(SASA): 0.0991
• 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
V/M	rs2154176354	None	0.997	N	0.707	0.554	0.70371367467	gnomAD-4.0.0	1.36885E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99688E-07	1.15958E-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
V/A	0.5226	ambiguous	0.5686	pathogenic	-1.536	Destabilizing	0.978	D	0.526	neutral	N	0.47737962	None	None	N
V/C	0.8625	likely_pathogenic	0.8785	pathogenic	-1.932	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
V/D	0.9881	likely_pathogenic	0.9908	pathogenic	-3.091	Highly Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
V/E	0.9789	likely_pathogenic	0.9827	pathogenic	-3.048	Highly Destabilizing	0.999	D	0.736	prob.delet.	D	0.537649961	None	None	N
V/F	0.9451	likely_pathogenic	0.9504	pathogenic	-1.333	Destabilizing	0.998	D	0.745	deleterious	None	None	None	None	N
V/G	0.8044	likely_pathogenic	0.8461	pathogenic	-1.859	Destabilizing	0.999	D	0.753	deleterious	D	0.537649961	None	None	N
V/H	0.9954	likely_pathogenic	0.9962	pathogenic	-1.383	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
V/I	0.1528	likely_benign	0.1409	benign	-0.708	Destabilizing	0.437	N	0.293	neutral	None	None	None	None	N
V/K	0.9872	likely_pathogenic	0.9899	pathogenic	-1.491	Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
V/L	0.7911	likely_pathogenic	0.7927	pathogenic	-0.708	Destabilizing	0.9	D	0.457	neutral	N	0.492309964	None	None	N
V/M	0.7086	likely_pathogenic	0.71	pathogenic	-0.796	Destabilizing	0.997	D	0.707	prob.neutral	N	0.507682422	None	None	N
V/N	0.944	likely_pathogenic	0.9535	pathogenic	-1.745	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
V/P	0.9514	likely_pathogenic	0.964	pathogenic	-0.956	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
V/Q	0.9772	likely_pathogenic	0.9814	pathogenic	-1.933	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
V/R	0.9783	likely_pathogenic	0.9828	pathogenic	-0.99	Destabilizing	0.999	D	0.786	deleterious	None	None	None	None	N
V/S	0.7106	likely_pathogenic	0.7482	pathogenic	-2.107	Highly Destabilizing	0.999	D	0.73	prob.delet.	None	None	None	None	N
V/T	0.5633	ambiguous	0.6049	pathogenic	-1.96	Destabilizing	0.992	D	0.651	neutral	None	None	None	None	N
V/W	0.9989	likely_pathogenic	0.999	pathogenic	-1.662	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
V/Y	0.9925	likely_pathogenic	0.9939	pathogenic	-1.302	Destabilizing	0.999	D	0.747	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.