TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29091	87496;87497;87498	chr2:178558083;178558082;178558081	chr2:179422810;179422809;179422808
N2AB	27450	82573;82574;82575	chr2:178558083;178558082;178558081	chr2:179422810;179422809;179422808
N2A	26523	79792;79793;79794	chr2:178558083;178558082;178558081	chr2:179422810;179422809;179422808
N2B	20026	60301;60302;60303	chr2:178558083;178558082;178558081	chr2:179422810;179422809;179422808
Novex-1	20151	60676;60677;60678	chr2:178558083;178558082;178558081	chr2:179422810;179422809;179422808
Novex-2	20218	60877;60878;60879	chr2:178558083;178558082;178558081	chr2:179422810;179422809;179422808
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-145
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.1581
• 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
F/S	None	None	1.0	D	0.791	0.619	0.78271780837	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	3.66327E-05

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
F/A	0.8605	likely_pathogenic	0.8992	pathogenic	-2.858	Highly Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
F/C	0.3495	ambiguous	0.439	ambiguous	-2.423	Highly Destabilizing	1.0	D	0.811	deleterious	N	0.486807179	None	None	N
F/D	0.9781	likely_pathogenic	0.9823	pathogenic	-2.48	Highly Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
F/E	0.9633	likely_pathogenic	0.969	pathogenic	-2.304	Highly Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
F/G	0.9393	likely_pathogenic	0.9541	pathogenic	-3.303	Highly Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
F/H	0.8314	likely_pathogenic	0.84	pathogenic	-1.801	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
F/I	0.235	likely_benign	0.291	benign	-1.441	Destabilizing	1.0	D	0.679	prob.neutral	N	0.444053693	None	None	N
F/K	0.9599	likely_pathogenic	0.9663	pathogenic	-2.222	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
F/L	0.8252	likely_pathogenic	0.8755	pathogenic	-1.441	Destabilizing	0.999	D	0.504	neutral	N	0.44253354	None	None	N
F/M	0.5201	ambiguous	0.5934	pathogenic	-1.389	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
F/N	0.9147	likely_pathogenic	0.9303	pathogenic	-2.501	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
F/P	0.9987	likely_pathogenic	0.9988	pathogenic	-1.919	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
F/Q	0.9238	likely_pathogenic	0.9344	pathogenic	-2.482	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
F/R	0.925	likely_pathogenic	0.9344	pathogenic	-1.634	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
F/S	0.8325	likely_pathogenic	0.874	pathogenic	-3.336	Highly Destabilizing	1.0	D	0.791	deleterious	D	0.523805343	None	None	N
F/T	0.7963	likely_pathogenic	0.8415	pathogenic	-3.039	Highly Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
F/V	0.2534	likely_benign	0.3198	benign	-1.919	Destabilizing	1.0	D	0.712	prob.delet.	N	0.390123208	None	None	N
F/W	0.5908	likely_pathogenic	0.595	pathogenic	-0.612	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
F/Y	0.2513	likely_benign	0.2395	benign	-0.962	Destabilizing	0.999	D	0.512	neutral	N	0.484033446	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.