TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31498	94717;94718;94719	chr2:178547033;178547032;178547031	chr2:179411760;179411759;179411758
N2AB	29857	89794;89795;89796	chr2:178547033;178547032;178547031	chr2:179411760;179411759;179411758
N2A	28930	87013;87014;87015	chr2:178547033;178547032;178547031	chr2:179411760;179411759;179411758
N2B	22433	67522;67523;67524	chr2:178547033;178547032;178547031	chr2:179411760;179411759;179411758
Novex-1	22558	67897;67898;67899	chr2:178547033;178547032;178547031	chr2:179411760;179411759;179411758
Novex-2	22625	68098;68099;68100	chr2:178547033;178547032;178547031	chr2:179411760;179411759;179411758
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-117
• Domain position: 91
• Structural Position: 124
• Q(SASA): 0.7392
• 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
S/L	rs1281357207	0.215	0.999	N	0.651	0.444	0.425970041486	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
S/L	rs1281357207	0.215	0.999	N	0.651	0.444	0.425970041486	gnomAD-4.0.0	1.36918E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.7999E-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	0.4594	ambiguous	0.4542	ambiguous	-0.661	Destabilizing	0.994	D	0.483	neutral	N	0.506381845	None	None	I
S/C	0.3181	likely_benign	0.2972	benign	-0.457	Destabilizing	1.0	D	0.627	neutral	None	None	None	None	I
S/D	0.994	likely_pathogenic	0.9947	pathogenic	-0.939	Destabilizing	0.998	D	0.68	prob.neutral	None	None	None	None	I
S/E	0.9978	likely_pathogenic	0.9979	pathogenic	-0.796	Destabilizing	0.998	D	0.679	prob.neutral	None	None	None	None	I
S/F	0.9906	likely_pathogenic	0.9922	pathogenic	-0.4	Destabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	I
S/G	0.5168	ambiguous	0.5316	ambiguous	-1.04	Destabilizing	0.998	D	0.495	neutral	None	None	None	None	I
S/H	0.9922	likely_pathogenic	0.9925	pathogenic	-1.426	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	I
S/I	0.9728	likely_pathogenic	0.9725	pathogenic	0.282	Stabilizing	0.999	D	0.623	neutral	None	None	None	None	I
S/K	0.9997	likely_pathogenic	0.9996	pathogenic	-0.5	Destabilizing	0.998	D	0.671	prob.neutral	None	None	None	None	I
S/L	0.8892	likely_pathogenic	0.8805	pathogenic	0.282	Stabilizing	0.999	D	0.651	prob.neutral	N	0.507240764	None	None	I
S/M	0.9276	likely_pathogenic	0.9246	pathogenic	0.22	Stabilizing	1.0	D	0.615	neutral	None	None	None	None	I
S/N	0.9599	likely_pathogenic	0.9581	pathogenic	-0.921	Destabilizing	0.998	D	0.687	prob.delet.	None	None	None	None	I
S/P	0.9949	likely_pathogenic	0.9952	pathogenic	0.004	Stabilizing	0.999	D	0.684	prob.delet.	N	0.517372983	None	None	I
S/Q	0.9952	likely_pathogenic	0.9949	pathogenic	-0.752	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	I
S/R	0.9992	likely_pathogenic	0.9992	pathogenic	-0.761	Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	I
S/T	0.2475	likely_benign	0.2214	benign	-0.679	Destabilizing	0.997	D	0.561	neutral	N	0.478060147	None	None	I
S/V	0.9105	likely_pathogenic	0.9062	pathogenic	0.004	Stabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	I
S/W	0.9953	likely_pathogenic	0.9961	pathogenic	-0.616	Destabilizing	1.0	D	0.669	prob.neutral	None	None	None	None	I
S/Y	0.9925	likely_pathogenic	0.9939	pathogenic	-0.218	Destabilizing	0.999	D	0.657	prob.neutral	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.