TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24184	72775;72776;72777	chr2:178573582;178573581;178573580	chr2:179438309;179438308;179438307
N2AB	22543	67852;67853;67854	chr2:178573582;178573581;178573580	chr2:179438309;179438308;179438307
N2A	21616	65071;65072;65073	chr2:178573582;178573581;178573580	chr2:179438309;179438308;179438307
N2B	15119	45580;45581;45582	chr2:178573582;178573581;178573580	chr2:179438309;179438308;179438307
Novex-1	15244	45955;45956;45957	chr2:178573582;178573581;178573580	chr2:179438309;179438308;179438307
Novex-2	15311	46156;46157;46158	chr2:178573582;178573581;178573580	chr2:179438309;179438308;179438307
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-63
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.1331
• 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/G	None	None	0.89	D	0.783	0.557	0.824973454226	gnomAD-4.0.0	1.48974E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.89278E-06	0	0
V/I	None	None	0.656	N	0.541	0.179	0.409533910539	gnomAD-4.0.0	1.95044E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.3743E-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
V/A	0.5617	ambiguous	0.6107	pathogenic	-1.857	Destabilizing	0.014	N	0.341	neutral	N	0.476024182	None	None	N
V/C	0.9119	likely_pathogenic	0.9288	pathogenic	-1.372	Destabilizing	0.994	D	0.761	deleterious	None	None	None	None	N
V/D	0.9914	likely_pathogenic	0.9909	pathogenic	-2.32	Highly Destabilizing	0.971	D	0.836	deleterious	N	0.505155575	None	None	N
V/E	0.9737	likely_pathogenic	0.9727	pathogenic	-2.112	Highly Destabilizing	0.956	D	0.813	deleterious	None	None	None	None	N
V/F	0.7476	likely_pathogenic	0.7617	pathogenic	-1.118	Destabilizing	0.971	D	0.751	deleterious	N	0.514292926	None	None	N
V/G	0.8419	likely_pathogenic	0.8537	pathogenic	-2.377	Highly Destabilizing	0.89	D	0.783	deleterious	D	0.555949621	None	None	N
V/H	0.9924	likely_pathogenic	0.9927	pathogenic	-2.061	Highly Destabilizing	0.998	D	0.855	deleterious	None	None	None	None	N
V/I	0.0968	likely_benign	0.0894	benign	-0.425	Destabilizing	0.656	D	0.541	neutral	N	0.486563958	None	None	N
V/K	0.9888	likely_pathogenic	0.9891	pathogenic	-1.695	Destabilizing	0.956	D	0.817	deleterious	None	None	None	None	N
V/L	0.5954	likely_pathogenic	0.607	pathogenic	-0.425	Destabilizing	0.489	N	0.663	neutral	N	0.473620056	None	None	N
V/M	0.5428	ambiguous	0.5595	ambiguous	-0.407	Destabilizing	0.993	D	0.716	prob.delet.	None	None	None	None	N
V/N	0.966	likely_pathogenic	0.9661	pathogenic	-1.983	Destabilizing	0.978	D	0.847	deleterious	None	None	None	None	N
V/P	0.9816	likely_pathogenic	0.9847	pathogenic	-0.873	Destabilizing	0.978	D	0.819	deleterious	None	None	None	None	N
V/Q	0.9766	likely_pathogenic	0.9775	pathogenic	-1.836	Destabilizing	0.978	D	0.833	deleterious	None	None	None	None	N
V/R	0.9843	likely_pathogenic	0.9846	pathogenic	-1.511	Destabilizing	0.956	D	0.831	deleterious	None	None	None	None	N
V/S	0.8831	likely_pathogenic	0.8953	pathogenic	-2.585	Highly Destabilizing	0.915	D	0.778	deleterious	None	None	None	None	N
V/T	0.7554	likely_pathogenic	0.7823	pathogenic	-2.225	Highly Destabilizing	0.86	D	0.64	neutral	None	None	None	None	N
V/W	0.9952	likely_pathogenic	0.9954	pathogenic	-1.595	Destabilizing	0.998	D	0.823	deleterious	None	None	None	None	N
V/Y	0.9688	likely_pathogenic	0.9723	pathogenic	-1.179	Destabilizing	0.993	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.