TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18556	55891;55892;55893	chr2:178601331;178601330;178601329	chr2:179466058;179466057;179466056
N2AB	16915	50968;50969;50970	chr2:178601331;178601330;178601329	chr2:179466058;179466057;179466056
N2A	15988	48187;48188;48189	chr2:178601331;178601330;178601329	chr2:179466058;179466057;179466056
N2B	9491	28696;28697;28698	chr2:178601331;178601330;178601329	chr2:179466058;179466057;179466056
Novex-1	9616	29071;29072;29073	chr2:178601331;178601330;178601329	chr2:179466058;179466057;179466056
Novex-2	9683	29272;29273;29274	chr2:178601331;178601330;178601329	chr2:179466058;179466057;179466056
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-22
• Domain position: 78
• Structural Position: 111
• Q(SASA): 0.2648
• 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
E/K	None	None	0.865	N	0.466	0.27	0.265929055128	gnomAD-4.0.0	3.20575E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.76356E-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
E/A	0.2064	likely_benign	0.1803	benign	-1.248	Destabilizing	0.865	D	0.575	neutral	N	0.466707522	None	None	N
E/C	0.7688	likely_pathogenic	0.7461	pathogenic	-0.957	Destabilizing	0.999	D	0.838	deleterious	None	None	None	None	N
E/D	0.6216	likely_pathogenic	0.6325	pathogenic	-1.549	Destabilizing	0.928	D	0.435	neutral	N	0.519756521	None	None	N
E/F	0.8187	likely_pathogenic	0.7967	pathogenic	-1.371	Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
E/G	0.3868	ambiguous	0.34	ambiguous	-1.591	Destabilizing	0.978	D	0.749	deleterious	N	0.490131376	None	None	N
E/H	0.6216	likely_pathogenic	0.5949	pathogenic	-1.512	Destabilizing	0.998	D	0.713	prob.delet.	None	None	None	None	N
E/I	0.334	likely_benign	0.3063	benign	-0.299	Destabilizing	0.992	D	0.882	deleterious	None	None	None	None	N
E/K	0.1993	likely_benign	0.1613	benign	-1.291	Destabilizing	0.865	D	0.466	neutral	N	0.468544401	None	None	N
E/L	0.5445	ambiguous	0.4894	ambiguous	-0.299	Destabilizing	0.983	D	0.837	deleterious	None	None	None	None	N
E/M	0.4507	ambiguous	0.4122	ambiguous	0.258	Stabilizing	0.998	D	0.845	deleterious	None	None	None	None	N
E/N	0.5552	ambiguous	0.5535	ambiguous	-1.466	Destabilizing	0.983	D	0.685	prob.neutral	None	None	None	None	N
E/P	0.9911	likely_pathogenic	0.9895	pathogenic	-0.597	Destabilizing	0.992	D	0.839	deleterious	None	None	None	None	N
E/Q	0.1013	likely_benign	0.0922	benign	-1.285	Destabilizing	0.284	N	0.233	neutral	N	0.464986002	None	None	N
E/R	0.3004	likely_benign	0.2536	benign	-1.221	Destabilizing	0.968	D	0.685	prob.neutral	None	None	None	None	N
E/S	0.2968	likely_benign	0.2846	benign	-2.03	Highly Destabilizing	0.895	D	0.521	neutral	None	None	None	None	N
E/T	0.2847	likely_benign	0.2775	benign	-1.712	Destabilizing	0.983	D	0.758	deleterious	None	None	None	None	N
E/V	0.1839	likely_benign	0.1611	benign	-0.597	Destabilizing	0.978	D	0.829	deleterious	N	0.461233078	None	None	N
E/W	0.9424	likely_pathogenic	0.9313	pathogenic	-1.486	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
E/Y	0.7963	likely_pathogenic	0.7698	pathogenic	-1.196	Destabilizing	0.992	D	0.867	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.