TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29805	89638;89639;89640	chr2:178553592;178553591;178553590	chr2:179418319;179418318;179418317
N2AB	28164	84715;84716;84717	chr2:178553592;178553591;178553590	chr2:179418319;179418318;179418317
N2A	27237	81934;81935;81936	chr2:178553592;178553591;178553590	chr2:179418319;179418318;179418317
N2B	20740	62443;62444;62445	chr2:178553592;178553591;178553590	chr2:179418319;179418318;179418317
Novex-1	20865	62818;62819;62820	chr2:178553592;178553591;178553590	chr2:179418319;179418318;179418317
Novex-2	20932	63019;63020;63021	chr2:178553592;178553591;178553590	chr2:179418319;179418318;179418317
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-105
• Domain position: 72
• Structural Position: 103
• Q(SASA): 0.4926
• 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/S	rs369285180	-0.618	0.027	N	0.402	0.206	None	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	3.56E-05	0
N/S	rs369285180	-0.618	0.027	N	0.402	0.206	None	gnomAD-3.1.2	3.28E-05	None	None	None	None	N	None	4.82E-05	0	0	0	0	None	0	0	4.41E-05	0	0
N/S	rs369285180	-0.618	0.027	N	0.402	0.206	None	gnomAD-4.0.0	1.04102E-04	None	None	None	None	N	None	5.33775E-05	0	None	0	0	None	0	0	1.39004E-04	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	0.2057	likely_benign	0.205	benign	-1.045	Destabilizing	0.149	N	0.484	neutral	None	None	None	None	N
N/C	0.2895	likely_benign	0.2855	benign	-0.051	Destabilizing	0.935	D	0.587	neutral	None	None	None	None	N
N/D	0.0936	likely_benign	0.0852	benign	-0.326	Destabilizing	None	N	0.115	neutral	N	0.437345859	None	None	N
N/E	0.2763	likely_benign	0.2707	benign	-0.186	Destabilizing	0.035	N	0.377	neutral	None	None	None	None	N
N/F	0.4994	ambiguous	0.47	ambiguous	-0.656	Destabilizing	0.081	N	0.579	neutral	None	None	None	None	N
N/G	0.3058	likely_benign	0.3077	benign	-1.413	Destabilizing	0.067	N	0.407	neutral	None	None	None	None	N
N/H	0.1237	likely_benign	0.1148	benign	-0.901	Destabilizing	None	N	0.199	neutral	N	0.472594583	None	None	N
N/I	0.2181	likely_benign	0.2139	benign	-0.085	Destabilizing	0.484	N	0.579	neutral	N	0.453739464	None	None	N
N/K	0.2941	likely_benign	0.2857	benign	-0.117	Destabilizing	0.117	N	0.381	neutral	N	0.419874819	None	None	N
N/L	0.2288	likely_benign	0.2337	benign	-0.085	Destabilizing	0.149	N	0.519	neutral	None	None	None	None	N
N/M	0.3449	ambiguous	0.3337	benign	0.247	Stabilizing	0.935	D	0.567	neutral	None	None	None	None	N
N/P	0.3232	likely_benign	0.3422	ambiguous	-0.376	Destabilizing	0.555	D	0.575	neutral	None	None	None	None	N
N/Q	0.3009	likely_benign	0.2998	benign	-0.621	Destabilizing	0.38	N	0.495	neutral	None	None	None	None	N
N/R	0.3418	ambiguous	0.3433	ambiguous	-0.175	Destabilizing	0.149	N	0.495	neutral	None	None	None	None	N
N/S	0.0876	likely_benign	0.0888	benign	-0.892	Destabilizing	0.027	N	0.402	neutral	N	0.393805726	None	None	N
N/T	0.135	likely_benign	0.1284	benign	-0.544	Destabilizing	0.117	N	0.381	neutral	N	0.416258511	None	None	N
N/V	0.2284	likely_benign	0.224	benign	-0.376	Destabilizing	0.149	N	0.561	neutral	None	None	None	None	N
N/W	0.6914	likely_pathogenic	0.6914	pathogenic	-0.357	Destabilizing	0.824	D	0.585	neutral	None	None	None	None	N
N/Y	0.1504	likely_benign	0.1364	benign	-0.154	Destabilizing	0.001	N	0.284	neutral	N	0.457491845	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.