TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7776	23551;23552;23553	chr2:178720436;178720435;178720434	chr2:179585163;179585162;179585161
N2AB	7459	22600;22601;22602	chr2:178720436;178720435;178720434	chr2:179585163;179585162;179585161
N2A	6532	19819;19820;19821	chr2:178720436;178720435;178720434	chr2:179585163;179585162;179585161
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-62
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.0843
• 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
A/T	None	None	0.999	D	0.655	0.548	0.551009825273	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
A/C	0.8943	likely_pathogenic	0.902	pathogenic	-1.517	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
A/D	0.9971	likely_pathogenic	0.9976	pathogenic	-2.757	Highly Destabilizing	1.0	D	0.851	deleterious	D	0.652466171	None	None	N
A/E	0.9918	likely_pathogenic	0.9934	pathogenic	-2.529	Highly Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
A/F	0.9386	likely_pathogenic	0.9486	pathogenic	-0.741	Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
A/G	0.5619	ambiguous	0.5726	pathogenic	-1.778	Destabilizing	0.965	D	0.653	neutral	D	0.584966979	None	None	N
A/H	0.9971	likely_pathogenic	0.9976	pathogenic	-2.156	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
A/I	0.4763	ambiguous	0.5282	ambiguous	0.019	Stabilizing	0.997	D	0.729	prob.delet.	None	None	None	None	N
A/K	0.9983	likely_pathogenic	0.9986	pathogenic	-1.27	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
A/L	0.5799	likely_pathogenic	0.6308	pathogenic	0.019	Stabilizing	0.979	D	0.724	prob.delet.	None	None	None	None	N
A/M	0.7746	likely_pathogenic	0.8128	pathogenic	-0.461	Destabilizing	0.999	D	0.821	deleterious	None	None	None	None	N
A/N	0.9906	likely_pathogenic	0.9922	pathogenic	-1.717	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
A/P	0.9919	likely_pathogenic	0.9931	pathogenic	-0.379	Destabilizing	1.0	D	0.829	deleterious	D	0.652264367	None	None	N
A/Q	0.9897	likely_pathogenic	0.9915	pathogenic	-1.464	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
A/R	0.9935	likely_pathogenic	0.9946	pathogenic	-1.425	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
A/S	0.5489	ambiguous	0.5692	pathogenic	-2.087	Highly Destabilizing	0.995	D	0.656	neutral	D	0.592426608	None	None	N
A/T	0.5482	ambiguous	0.5896	pathogenic	-1.734	Destabilizing	0.999	D	0.655	neutral	D	0.635639593	None	None	N
A/V	0.1802	likely_benign	0.1976	benign	-0.379	Destabilizing	0.484	N	0.305	neutral	D	0.530603603	None	None	N
A/W	0.998	likely_pathogenic	0.9984	pathogenic	-1.534	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
A/Y	0.9876	likely_pathogenic	0.99	pathogenic	-1.025	Destabilizing	1.0	D	0.849	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.