TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26145	78658;78659;78660	chr2:178567699;178567698;178567697	chr2:179432426;179432425;179432424
N2AB	24504	73735;73736;73737	chr2:178567699;178567698;178567697	chr2:179432426;179432425;179432424
N2A	23577	70954;70955;70956	chr2:178567699;178567698;178567697	chr2:179432426;179432425;179432424
N2B	17080	51463;51464;51465	chr2:178567699;178567698;178567697	chr2:179432426;179432425;179432424
Novex-1	17205	51838;51839;51840	chr2:178567699;178567698;178567697	chr2:179432426;179432425;179432424
Novex-2	17272	52039;52040;52041	chr2:178567699;178567698;178567697	chr2:179432426;179432425;179432424
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-78
• Domain position: 58
• Structural Position: 88
• Q(SASA): 0.3862
• 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
E/K	rs1405668603	0.413	0.939	N	0.487	0.32	0.303781844768	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.95E-06	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
E/A	0.3707	ambiguous	0.3595	ambiguous	-0.227	Destabilizing	0.939	D	0.56	neutral	N	0.48040599	None	None	I
E/C	0.9597	likely_pathogenic	0.9533	pathogenic	-0.374	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	I
E/D	0.1021	likely_benign	0.1006	benign	-0.488	Destabilizing	0.02	N	0.135	neutral	N	0.41712809	None	None	I
E/F	0.9618	likely_pathogenic	0.9527	pathogenic	0.183	Stabilizing	0.999	D	0.623	neutral	None	None	None	None	I
E/G	0.3186	likely_benign	0.3037	benign	-0.463	Destabilizing	0.939	D	0.507	neutral	N	0.503938998	None	None	I
E/H	0.7702	likely_pathogenic	0.758	pathogenic	0.641	Stabilizing	0.999	D	0.599	neutral	None	None	None	None	I
E/I	0.8689	likely_pathogenic	0.8566	pathogenic	0.373	Stabilizing	0.993	D	0.646	neutral	None	None	None	None	I
E/K	0.4644	ambiguous	0.4709	ambiguous	0.237	Stabilizing	0.939	D	0.487	neutral	N	0.496548879	None	None	I
E/L	0.8347	likely_pathogenic	0.8152	pathogenic	0.373	Stabilizing	0.993	D	0.639	neutral	None	None	None	None	I
E/M	0.847	likely_pathogenic	0.8265	pathogenic	0.161	Stabilizing	0.999	D	0.611	neutral	None	None	None	None	I
E/N	0.3436	ambiguous	0.3319	benign	-0.343	Destabilizing	0.973	D	0.566	neutral	None	None	None	None	I
E/P	0.9622	likely_pathogenic	0.9636	pathogenic	0.193	Stabilizing	0.993	D	0.655	neutral	None	None	None	None	I
E/Q	0.3349	likely_benign	0.3305	benign	-0.248	Destabilizing	0.991	D	0.555	neutral	N	0.503090849	None	None	I
E/R	0.6672	likely_pathogenic	0.6637	pathogenic	0.65	Stabilizing	0.993	D	0.614	neutral	None	None	None	None	I
E/S	0.3521	ambiguous	0.3339	benign	-0.481	Destabilizing	0.953	D	0.495	neutral	None	None	None	None	I
E/T	0.4907	ambiguous	0.4824	ambiguous	-0.273	Destabilizing	0.993	D	0.604	neutral	None	None	None	None	I
E/V	0.6881	likely_pathogenic	0.6713	pathogenic	0.193	Stabilizing	0.991	D	0.616	neutral	N	0.509440818	None	None	I
E/W	0.9881	likely_pathogenic	0.9856	pathogenic	0.379	Stabilizing	0.999	D	0.665	neutral	None	None	None	None	I
E/Y	0.9114	likely_pathogenic	0.8982	pathogenic	0.444	Stabilizing	0.999	D	0.61	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.