TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6900	20923;20924;20925	chr2:178725506;178725505;178725504	chr2:179590233;179590232;179590231
N2AB	6583	19972;19973;19974	chr2:178725506;178725505;178725504	chr2:179590233;179590232;179590231
N2A	5656	17191;17192;17193	chr2:178725506;178725505;178725504	chr2:179590233;179590232;179590231
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: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-53
• Domain position: 47
• Structural Position: 115
• Q(SASA): 0.3629
• 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
N/K	None	None	0.998	N	0.564	0.197	0.0920862733494	gnomAD-4.0.0	3.42199E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49822E-06	0	0
N/S	rs1389235832	None	0.998	N	0.383	0.217	0.117506650769	gnomAD-4.0.0	1.59226E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86015E-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
N/A	0.4198	ambiguous	0.4062	ambiguous	-0.799	Destabilizing	0.998	D	0.603	neutral	None	None	None	None	N
N/C	0.5936	likely_pathogenic	0.5772	pathogenic	0.139	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
N/D	0.1619	likely_benign	0.1579	benign	0.087	Stabilizing	0.998	D	0.441	neutral	N	0.508656092	None	None	N
N/E	0.5365	ambiguous	0.5344	ambiguous	0.116	Stabilizing	0.997	D	0.516	neutral	None	None	None	None	N
N/F	0.722	likely_pathogenic	0.7024	pathogenic	-0.831	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
N/G	0.4107	ambiguous	0.3788	ambiguous	-1.062	Destabilizing	0.998	D	0.393	neutral	None	None	None	None	N
N/H	0.2132	likely_benign	0.2015	benign	-0.893	Destabilizing	0.64	D	0.273	neutral	N	0.459286512	None	None	N
N/I	0.3836	ambiguous	0.3918	ambiguous	-0.162	Destabilizing	1.0	D	0.739	prob.delet.	N	0.478151235	None	None	N
N/K	0.495	ambiguous	0.507	ambiguous	-0.045	Destabilizing	0.998	D	0.564	neutral	N	0.448749446	None	None	N
N/L	0.4654	ambiguous	0.4587	ambiguous	-0.162	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
N/M	0.4829	ambiguous	0.466	ambiguous	0.304	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	N
N/P	0.8592	likely_pathogenic	0.8532	pathogenic	-0.345	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
N/Q	0.5423	ambiguous	0.5289	ambiguous	-0.595	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	N
N/R	0.5815	likely_pathogenic	0.5944	pathogenic	-0.019	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	N
N/S	0.1683	likely_benign	0.1625	benign	-0.543	Destabilizing	0.998	D	0.383	neutral	N	0.457387181	None	None	N
N/T	0.2226	likely_benign	0.2155	benign	-0.332	Destabilizing	0.999	D	0.566	neutral	N	0.468996976	None	None	N
N/V	0.4369	ambiguous	0.4399	ambiguous	-0.345	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
N/W	0.8922	likely_pathogenic	0.8854	pathogenic	-0.618	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
N/Y	0.2561	likely_benign	0.2454	benign	-0.423	Destabilizing	0.999	D	0.663	neutral	N	0.469757444	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.