TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14017	42274;42275;42276	chr2:178634825;178634824;178634823	chr2:179499552;179499551;179499550
N2AB	12376	37351;37352;37353	chr2:178634825;178634824;178634823	chr2:179499552;179499551;179499550
N2A	11449	34570;34571;34572	chr2:178634825;178634824;178634823	chr2:179499552;179499551;179499550
N2B	4952	15079;15080;15081	chr2:178634825;178634824;178634823	chr2:179499552;179499551;179499550
Novex-1	5077	15454;15455;15456	chr2:178634825;178634824;178634823	chr2:179499552;179499551;179499550
Novex-2	5144	15655;15656;15657	chr2:178634825;178634824;178634823	chr2:179499552;179499551;179499550
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-90
• Domain position: 53
• Structural Position: 134
• Q(SASA): 0.216
• 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
G/R	rs1161979802	None	0.034	N	0.511	0.194	0.233785782151	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
G/R	rs1161979802	None	0.034	N	0.511	0.194	0.233785782151	gnomAD-4.0.0	2.57034E-06	None	None	None	None	N	None	1.69607E-05	0	None	0	0	None	0	0	2.39741E-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
G/A	0.3585	ambiguous	0.2558	benign	-0.855	Destabilizing	0.919	D	0.545	neutral	N	0.441258993	None	None	N
G/C	0.5536	ambiguous	0.4502	ambiguous	-1.138	Destabilizing	0.999	D	0.76	deleterious	None	None	None	None	N
G/D	0.4186	ambiguous	0.3528	ambiguous	-1.443	Destabilizing	0.883	D	0.705	prob.delet.	None	None	None	None	N
G/E	0.5126	ambiguous	0.4119	ambiguous	-1.521	Destabilizing	0.919	D	0.679	prob.neutral	N	0.426698874	None	None	N
G/F	0.8885	likely_pathogenic	0.8224	pathogenic	-1.246	Destabilizing	0.997	D	0.767	deleterious	None	None	None	None	N
G/H	0.7301	likely_pathogenic	0.5993	pathogenic	-1.264	Destabilizing	0.991	D	0.733	deleterious	None	None	None	None	N
G/I	0.7286	likely_pathogenic	0.5836	pathogenic	-0.593	Destabilizing	0.997	D	0.784	deleterious	None	None	None	None	N
G/K	0.6937	likely_pathogenic	0.5335	ambiguous	-1.286	Destabilizing	0.168	N	0.543	neutral	None	None	None	None	N
G/L	0.7936	likely_pathogenic	0.6667	pathogenic	-0.593	Destabilizing	0.991	D	0.668	prob.neutral	None	None	None	None	N
G/M	0.7822	likely_pathogenic	0.6408	pathogenic	-0.521	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
G/N	0.3765	ambiguous	0.2687	benign	-1.019	Destabilizing	0.319	N	0.31	neutral	None	None	None	None	N
G/P	0.925	likely_pathogenic	0.8647	pathogenic	-0.642	Destabilizing	0.997	D	0.761	deleterious	None	None	None	None	N
G/Q	0.5424	ambiguous	0.4103	ambiguous	-1.277	Destabilizing	0.981	D	0.682	prob.neutral	None	None	None	None	N
G/R	0.5935	likely_pathogenic	0.4471	ambiguous	-0.888	Destabilizing	0.034	N	0.511	neutral	N	0.425628763	None	None	N
G/S	0.208	likely_benign	0.146	benign	-1.249	Destabilizing	0.938	D	0.587	neutral	None	None	None	None	N
G/T	0.4044	ambiguous	0.2457	benign	-1.26	Destabilizing	0.938	D	0.697	prob.delet.	None	None	None	None	N
G/V	0.6361	likely_pathogenic	0.4793	ambiguous	-0.642	Destabilizing	0.988	D	0.736	deleterious	N	0.429565586	None	None	N
G/W	0.7938	likely_pathogenic	0.7092	pathogenic	-1.507	Destabilizing	0.999	D	0.714	prob.delet.	None	None	None	None	N
G/Y	0.797	likely_pathogenic	0.7063	pathogenic	-1.135	Destabilizing	0.997	D	0.779	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.