TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21849	65770;65771;65772	chr2:178583637;178583636;178583635	chr2:179448364;179448363;179448362
N2AB	20208	60847;60848;60849	chr2:178583637;178583636;178583635	chr2:179448364;179448363;179448362
N2A	19281	58066;58067;58068	chr2:178583637;178583636;178583635	chr2:179448364;179448363;179448362
N2B	12784	38575;38576;38577	chr2:178583637;178583636;178583635	chr2:179448364;179448363;179448362
Novex-1	12909	38950;38951;38952	chr2:178583637;178583636;178583635	chr2:179448364;179448363;179448362
Novex-2	12976	39151;39152;39153	chr2:178583637;178583636;178583635	chr2:179448364;179448363;179448362
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-46
• Domain position: 93
• Structural Position: 124
• Q(SASA): 0.1017
• 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
S/F	rs1060500465	None	0.999	N	0.886	0.396	0.58951732002	gnomAD-4.0.0	3.20569E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.76073E-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
S/A	0.2796	likely_benign	0.2192	benign	-0.622	Destabilizing	0.994	D	0.685	prob.delet.	N	0.480871304	None	None	N
S/C	0.3384	likely_benign	0.2672	benign	-0.518	Destabilizing	1.0	D	0.723	deleterious	N	0.50306739	None	None	N
S/D	0.9797	likely_pathogenic	0.9725	pathogenic	-1.342	Destabilizing	0.998	D	0.588	neutral	None	None	None	None	N
S/E	0.9904	likely_pathogenic	0.9864	pathogenic	-1.185	Destabilizing	0.998	D	0.564	neutral	None	None	None	None	N
S/F	0.9735	likely_pathogenic	0.9507	pathogenic	-0.346	Destabilizing	0.999	D	0.886	deleterious	N	0.508636797	None	None	N
S/G	0.3386	likely_benign	0.2786	benign	-1.01	Destabilizing	0.998	D	0.656	prob.neutral	None	None	None	None	N
S/H	0.9824	likely_pathogenic	0.9776	pathogenic	-1.496	Destabilizing	1.0	D	0.732	deleterious	None	None	None	None	N
S/I	0.8781	likely_pathogenic	0.7859	pathogenic	0.35	Stabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
S/K	0.9982	likely_pathogenic	0.9973	pathogenic	-0.632	Destabilizing	0.998	D	0.577	neutral	None	None	None	None	N
S/L	0.6279	likely_pathogenic	0.5099	ambiguous	0.35	Stabilizing	0.999	D	0.723	deleterious	None	None	None	None	N
S/M	0.7911	likely_pathogenic	0.6809	pathogenic	0.288	Stabilizing	1.0	D	0.727	deleterious	None	None	None	None	N
S/N	0.9027	likely_pathogenic	0.8688	pathogenic	-1.159	Destabilizing	0.998	D	0.609	neutral	None	None	None	None	N
S/P	0.9819	likely_pathogenic	0.9756	pathogenic	0.062	Stabilizing	0.999	D	0.745	deleterious	N	0.49804096	None	None	N
S/Q	0.9856	likely_pathogenic	0.9804	pathogenic	-0.932	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
S/R	0.9957	likely_pathogenic	0.994	pathogenic	-0.954	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
S/T	0.1249	likely_benign	0.0958	benign	-0.82	Destabilizing	0.997	D	0.669	prob.neutral	N	0.467817908	None	None	N
S/V	0.7531	likely_pathogenic	0.6222	pathogenic	0.062	Stabilizing	0.999	D	0.845	deleterious	None	None	None	None	N
S/W	0.9824	likely_pathogenic	0.9732	pathogenic	-0.655	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
S/Y	0.9734	likely_pathogenic	0.9587	pathogenic	-0.23	Destabilizing	0.999	D	0.894	deleterious	N	0.520246592	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.