TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30689	92290;92291;92292	chr2:178549657;178549656;178549655	chr2:179414384;179414383;179414382
N2AB	29048	87367;87368;87369	chr2:178549657;178549656;178549655	chr2:179414384;179414383;179414382
N2A	28121	84586;84587;84588	chr2:178549657;178549656;178549655	chr2:179414384;179414383;179414382
N2B	21624	65095;65096;65097	chr2:178549657;178549656;178549655	chr2:179414384;179414383;179414382
Novex-1	21749	65470;65471;65472	chr2:178549657;178549656;178549655	chr2:179414384;179414383;179414382
Novex-2	21816	65671;65672;65673	chr2:178549657;178549656;178549655	chr2:179414384;179414383;179414382
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: Fn3-111
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.332
• 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/Q	None	None	1.0	N	0.628	0.355	0.294206760003	gnomAD-4.0.0	1.36843E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9948E-07	0	1.65667E-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
E/A	0.4694	ambiguous	0.5389	ambiguous	-1.076	Destabilizing	0.999	D	0.713	prob.delet.	N	0.498413489	None	None	N
E/C	0.961	likely_pathogenic	0.9688	pathogenic	-0.579	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/D	0.7018	likely_pathogenic	0.7413	pathogenic	-1.185	Destabilizing	0.999	D	0.478	neutral	N	0.483752275	None	None	N
E/F	0.9744	likely_pathogenic	0.9795	pathogenic	-0.515	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/G	0.7385	likely_pathogenic	0.7926	pathogenic	-1.473	Destabilizing	1.0	D	0.76	deleterious	N	0.512011521	None	None	N
E/H	0.8894	likely_pathogenic	0.9127	pathogenic	-0.849	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
E/I	0.7322	likely_pathogenic	0.7862	pathogenic	0.026	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/K	0.5275	ambiguous	0.6065	pathogenic	-0.868	Destabilizing	0.999	D	0.617	neutral	N	0.486345941	None	None	N
E/L	0.8434	likely_pathogenic	0.8781	pathogenic	0.026	Stabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
E/M	0.8132	likely_pathogenic	0.8487	pathogenic	0.59	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
E/N	0.7877	likely_pathogenic	0.8222	pathogenic	-1.284	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
E/P	0.9544	likely_pathogenic	0.9706	pathogenic	-0.321	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/Q	0.3242	likely_benign	0.3449	ambiguous	-1.123	Destabilizing	1.0	D	0.628	neutral	N	0.477320267	None	None	N
E/R	0.673	likely_pathogenic	0.7237	pathogenic	-0.628	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
E/S	0.6115	likely_pathogenic	0.6606	pathogenic	-1.716	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
E/T	0.598	likely_pathogenic	0.6613	pathogenic	-1.378	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/V	0.5637	ambiguous	0.6306	pathogenic	-0.321	Destabilizing	1.0	D	0.794	deleterious	N	0.490869072	None	None	N
E/W	0.9936	likely_pathogenic	0.9954	pathogenic	-0.278	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
E/Y	0.9514	likely_pathogenic	0.9633	pathogenic	-0.258	Destabilizing	1.0	D	0.776	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.