TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25265	76018;76019;76020	chr2:178570339;178570338;178570337	chr2:179435066;179435065;179435064
N2AB	23624	71095;71096;71097	chr2:178570339;178570338;178570337	chr2:179435066;179435065;179435064
N2A	22697	68314;68315;68316	chr2:178570339;178570338;178570337	chr2:179435066;179435065;179435064
N2B	16200	48823;48824;48825	chr2:178570339;178570338;178570337	chr2:179435066;179435065;179435064
Novex-1	16325	49198;49199;49200	chr2:178570339;178570338;178570337	chr2:179435066;179435065;179435064
Novex-2	16392	49399;49400;49401	chr2:178570339;178570338;178570337	chr2:179435066;179435065;179435064
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-71
• Domain position: 62
• Structural Position: 92
• Q(SASA): 0.3899
• 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
K/N	None	None	0.967	N	0.615	0.273	0.184867976434	gnomAD-4.0.0	6.84426E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99596E-07	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
K/A	0.7271	likely_pathogenic	0.8158	pathogenic	None	Stabilizing	0.845	D	0.57	neutral	None	None	None	None	N
K/C	0.8393	likely_pathogenic	0.8991	pathogenic	-0.073	Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
K/D	0.9052	likely_pathogenic	0.936	pathogenic	0.045	Stabilizing	0.975	D	0.733	prob.delet.	None	None	None	None	N
K/E	0.6356	likely_pathogenic	0.7422	pathogenic	0.063	Stabilizing	0.892	D	0.464	neutral	N	0.515131852	None	None	N
K/F	0.9448	likely_pathogenic	0.9645	pathogenic	-0.1	Destabilizing	0.987	D	0.777	deleterious	None	None	None	None	N
K/G	0.8306	likely_pathogenic	0.8835	pathogenic	-0.235	Destabilizing	0.975	D	0.722	prob.delet.	None	None	None	None	N
K/H	0.4844	ambiguous	0.5838	pathogenic	-0.545	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
K/I	0.6145	likely_pathogenic	0.7096	pathogenic	0.549	Stabilizing	0.975	D	0.776	deleterious	None	None	None	None	N
K/L	0.6886	likely_pathogenic	0.7798	pathogenic	0.549	Stabilizing	0.845	D	0.677	prob.neutral	None	None	None	None	N
K/M	0.5167	ambiguous	0.6331	pathogenic	0.356	Stabilizing	0.999	D	0.733	prob.delet.	N	0.483472332	None	None	N
K/N	0.8073	likely_pathogenic	0.8687	pathogenic	0.273	Stabilizing	0.967	D	0.615	neutral	N	0.500567832	None	None	N
K/P	0.8959	likely_pathogenic	0.9321	pathogenic	0.395	Stabilizing	0.987	D	0.759	deleterious	None	None	None	None	N
K/Q	0.3188	likely_benign	0.4171	ambiguous	0.098	Stabilizing	0.983	D	0.599	neutral	N	0.469545132	None	None	N
K/R	0.0913	likely_benign	0.0954	benign	-0.065	Destabilizing	0.892	D	0.503	neutral	N	0.512496979	None	None	N
K/S	0.763	likely_pathogenic	0.8424	pathogenic	-0.219	Destabilizing	0.845	D	0.481	neutral	None	None	None	None	N
K/T	0.3673	ambiguous	0.4873	ambiguous	-0.045	Destabilizing	0.025	N	0.388	neutral	N	0.444900976	None	None	N
K/V	0.5422	ambiguous	0.6388	pathogenic	0.395	Stabilizing	0.95	D	0.719	prob.delet.	None	None	None	None	N
K/W	0.8945	likely_pathogenic	0.9356	pathogenic	-0.094	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
K/Y	0.8618	likely_pathogenic	0.903	pathogenic	0.243	Stabilizing	0.996	D	0.787	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.