TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27305	82138;82139;82140	chr2:178564219;178564218;178564217	chr2:179428946;179428945;179428944
N2AB	25664	77215;77216;77217	chr2:178564219;178564218;178564217	chr2:179428946;179428945;179428944
N2A	24737	74434;74435;74436	chr2:178564219;178564218;178564217	chr2:179428946;179428945;179428944
N2B	18240	54943;54944;54945	chr2:178564219;178564218;178564217	chr2:179428946;179428945;179428944
Novex-1	18365	55318;55319;55320	chr2:178564219;178564218;178564217	chr2:179428946;179428945;179428944
Novex-2	18432	55519;55520;55521	chr2:178564219;178564218;178564217	chr2:179428946;179428945;179428944
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-140
• Domain position: 28
• Structural Position: 44
• Q(SASA): 0.1502
• 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
P/S	rs1704786507	None	1.0	D	0.839	0.623	0.595673181824	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/S	rs1704786507	None	1.0	D	0.839	0.623	0.595673181824	gnomAD-4.0.0	2.03004E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.40987E-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
P/A	0.7777	likely_pathogenic	0.7224	pathogenic	-1.583	Destabilizing	1.0	D	0.791	deleterious	D	0.542956334	None	None	N
P/C	0.9767	likely_pathogenic	0.9727	pathogenic	-1.292	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
P/D	0.9994	likely_pathogenic	0.9992	pathogenic	-1.332	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
P/E	0.998	likely_pathogenic	0.9969	pathogenic	-1.326	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
P/F	0.9985	likely_pathogenic	0.998	pathogenic	-1.327	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
P/G	0.9886	likely_pathogenic	0.985	pathogenic	-1.906	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
P/H	0.996	likely_pathogenic	0.9944	pathogenic	-1.456	Destabilizing	1.0	D	0.821	deleterious	D	0.576571177	None	None	N
P/I	0.9809	likely_pathogenic	0.9748	pathogenic	-0.792	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
P/K	0.9986	likely_pathogenic	0.9978	pathogenic	-1.198	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
P/L	0.9217	likely_pathogenic	0.8885	pathogenic	-0.792	Destabilizing	1.0	D	0.847	deleterious	D	0.553397132	None	None	N
P/M	0.9887	likely_pathogenic	0.984	pathogenic	-0.693	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
P/N	0.9989	likely_pathogenic	0.9985	pathogenic	-1.025	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
P/Q	0.9941	likely_pathogenic	0.9917	pathogenic	-1.203	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
P/R	0.9928	likely_pathogenic	0.9902	pathogenic	-0.732	Destabilizing	1.0	D	0.857	deleterious	D	0.576064198	None	None	N
P/S	0.9763	likely_pathogenic	0.9693	pathogenic	-1.61	Destabilizing	1.0	D	0.839	deleterious	D	0.575557219	None	None	N
P/T	0.957	likely_pathogenic	0.9393	pathogenic	-1.487	Destabilizing	1.0	D	0.846	deleterious	D	0.575557219	None	None	N
P/V	0.9546	likely_pathogenic	0.9419	pathogenic	-1.021	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
P/W	0.9993	likely_pathogenic	0.9989	pathogenic	-1.479	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
P/Y	0.9989	likely_pathogenic	0.9985	pathogenic	-1.177	Destabilizing	1.0	D	0.845	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.