TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6076	18451;18452;18453	chr2:178730174;178730173;178730172	chr2:179594901;179594900;179594899
N2AB	5759	17500;17501;17502	chr2:178730174;178730173;178730172	chr2:179594901;179594900;179594899
N2A	4832	14719;14720;14721	chr2:178730174;178730173;178730172	chr2:179594901;179594900;179594899
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: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-44
• Domain position: 65
• Structural Position: 146
• Q(SASA): 0.5245
• 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
A/S	rs371110666	-0.076	None	N	0.071	0.048	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
A/S	rs371110666	-0.076	None	N	0.071	0.048	None	gnomAD-4.0.0	6.8435E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99541E-07	0	0
A/T	None	None	None	N	0.073	0.052	0.0551355673512	gnomAD-4.0.0	1.3687E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79908E-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
A/C	0.4697	ambiguous	0.4856	ambiguous	-0.706	Destabilizing	0.356	N	0.303	neutral	None	None	None	None	N
A/D	0.2013	likely_benign	0.2079	benign	-0.378	Destabilizing	0.029	N	0.329	neutral	N	0.487878175	None	None	N
A/E	0.1635	likely_benign	0.1756	benign	-0.533	Destabilizing	0.016	N	0.295	neutral	None	None	None	None	N
A/F	0.2337	likely_benign	0.2619	benign	-0.933	Destabilizing	0.214	N	0.485	neutral	None	None	None	None	N
A/G	0.1129	likely_benign	0.119	benign	-0.357	Destabilizing	0.012	N	0.189	neutral	N	0.487878175	None	None	N
A/H	0.3476	ambiguous	0.3608	ambiguous	-0.415	Destabilizing	0.214	N	0.405	neutral	None	None	None	None	N
A/I	0.1191	likely_benign	0.1333	benign	-0.337	Destabilizing	None	N	0.199	neutral	None	None	None	None	N
A/K	0.2386	likely_benign	0.2488	benign	-0.564	Destabilizing	0.016	N	0.29	neutral	None	None	None	None	N
A/L	0.1068	likely_benign	0.1195	benign	-0.337	Destabilizing	0.002	N	0.283	neutral	None	None	None	None	N
A/M	0.1334	likely_benign	0.1502	benign	-0.288	Destabilizing	0.007	N	0.211	neutral	None	None	None	None	N
A/N	0.1449	likely_benign	0.1568	benign	-0.223	Destabilizing	None	N	0.197	neutral	None	None	None	None	N
A/P	0.0959	likely_benign	0.1021	benign	-0.289	Destabilizing	None	N	0.201	neutral	N	0.391060917	None	None	N
A/Q	0.2233	likely_benign	0.2335	benign	-0.516	Destabilizing	0.003	N	0.191	neutral	None	None	None	None	N
A/R	0.2462	likely_benign	0.2615	benign	-0.11	Destabilizing	0.072	N	0.337	neutral	None	None	None	None	N
A/S	0.0846	likely_benign	0.0876	benign	-0.454	Destabilizing	None	N	0.071	neutral	N	0.437083995	None	None	N
A/T	0.0706	likely_benign	0.0718	benign	-0.528	Destabilizing	None	N	0.073	neutral	N	0.420383747	None	None	N
A/V	0.0764	likely_benign	0.0834	benign	-0.289	Destabilizing	None	N	0.125	neutral	N	0.452282734	None	None	N
A/W	0.5518	ambiguous	0.5981	pathogenic	-1.068	Destabilizing	0.864	D	0.423	neutral	None	None	None	None	N
A/Y	0.3219	likely_benign	0.3438	ambiguous	-0.707	Destabilizing	0.356	N	0.466	neutral	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.