TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33323	100192;100193;100194	chr2:178537142;178537141;178537140	chr2:179401869;179401868;179401867
N2AB	31682	95269;95270;95271	chr2:178537142;178537141;178537140	chr2:179401869;179401868;179401867
N2A	30755	92488;92489;92490	chr2:178537142;178537141;178537140	chr2:179401869;179401868;179401867
N2B	24258	72997;72998;72999	chr2:178537142;178537141;178537140	chr2:179401869;179401868;179401867
Novex-1	24383	73372;73373;73374	chr2:178537142;178537141;178537140	chr2:179401869;179401868;179401867
Novex-2	24450	73573;73574;73575	chr2:178537142;178537141;178537140	chr2:179401869;179401868;179401867
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-130
• Domain position: 34
• Structural Position: 35
• Q(SASA): 0.133
• Predicted PPI site: I

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
I/F	rs1453366713	-1.747	0.991	D	0.75	0.476	0.78845046722	gnomAD-2.1.1	8.06E-06	None	None	None	None	I	None	0	5.81E-05	None	0	0	None	0	None	0	0	0
I/F	rs1453366713	-1.747	0.991	D	0.75	0.476	0.78845046722	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
I/F	rs1453366713	-1.747	0.991	D	0.75	0.476	0.78845046722	gnomAD-4.0.0	3.84423E-06	None	None	None	None	I	None	0	5.08699E-05	None	0	0	None	0	0	0	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
I/A	0.9892	likely_pathogenic	0.9865	pathogenic	-2.369	Highly Destabilizing	0.91	D	0.669	neutral	None	None	None	None	I
I/C	0.9915	likely_pathogenic	0.9891	pathogenic	-1.667	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	I
I/D	0.9989	likely_pathogenic	0.9984	pathogenic	-2.318	Highly Destabilizing	0.998	D	0.829	deleterious	None	None	None	None	I
I/E	0.995	likely_pathogenic	0.993	pathogenic	-2.236	Highly Destabilizing	0.993	D	0.82	deleterious	None	None	None	None	I
I/F	0.9712	likely_pathogenic	0.9395	pathogenic	-1.71	Destabilizing	0.991	D	0.75	deleterious	D	0.550047364	None	None	I
I/G	0.998	likely_pathogenic	0.997	pathogenic	-2.789	Highly Destabilizing	0.993	D	0.823	deleterious	None	None	None	None	I
I/H	0.9981	likely_pathogenic	0.9964	pathogenic	-2.057	Highly Destabilizing	0.999	D	0.784	deleterious	None	None	None	None	I
I/K	0.9902	likely_pathogenic	0.9821	pathogenic	-1.729	Destabilizing	0.993	D	0.819	deleterious	None	None	None	None	I
I/L	0.6494	likely_pathogenic	0.5995	pathogenic	-1.222	Destabilizing	0.58	D	0.457	neutral	N	0.480579632	None	None	I
I/M	0.7252	likely_pathogenic	0.6433	pathogenic	-0.956	Destabilizing	0.991	D	0.718	prob.delet.	D	0.552582259	None	None	I
I/N	0.9739	likely_pathogenic	0.963	pathogenic	-1.736	Destabilizing	0.997	D	0.823	deleterious	D	0.535491962	None	None	I
I/P	0.9821	likely_pathogenic	0.9755	pathogenic	-1.579	Destabilizing	0.998	D	0.827	deleterious	None	None	None	None	I
I/Q	0.9937	likely_pathogenic	0.9904	pathogenic	-1.848	Destabilizing	0.998	D	0.819	deleterious	None	None	None	None	I
I/R	0.9899	likely_pathogenic	0.981	pathogenic	-1.143	Destabilizing	0.998	D	0.824	deleterious	None	None	None	None	I
I/S	0.9899	likely_pathogenic	0.9871	pathogenic	-2.412	Highly Destabilizing	0.991	D	0.8	deleterious	D	0.541314859	None	None	I
I/T	0.9803	likely_pathogenic	0.9781	pathogenic	-2.202	Highly Destabilizing	0.939	D	0.778	deleterious	D	0.541314859	None	None	I
I/V	0.2218	likely_benign	0.2133	benign	-1.579	Destabilizing	0.02	N	0.255	neutral	N	0.475855917	None	None	I
I/W	0.9993	likely_pathogenic	0.9984	pathogenic	-1.91	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	I
I/Y	0.9953	likely_pathogenic	0.9903	pathogenic	-1.678	Destabilizing	0.998	D	0.775	deleterious	None	None	None	None	I

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.