TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27464	82615;82616;82617	chr2:178563742;178563741;178563740	chr2:179428469;179428468;179428467
N2AB	25823	77692;77693;77694	chr2:178563742;178563741;178563740	chr2:179428469;179428468;179428467
N2A	24896	74911;74912;74913	chr2:178563742;178563741;178563740	chr2:179428469;179428468;179428467
N2B	18399	55420;55421;55422	chr2:178563742;178563741;178563740	chr2:179428469;179428468;179428467
Novex-1	18524	55795;55796;55797	chr2:178563742;178563741;178563740	chr2:179428469;179428468;179428467
Novex-2	18591	55996;55997;55998	chr2:178563742;178563741;178563740	chr2:179428469;179428468;179428467
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-87
• Domain position: 96
• Structural Position: 131
• Q(SASA): 0.391
• 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
C/R	rs1704578437	None	None	N	0.075	0.154	0.199424873507	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
C/R	rs1704578437	None	None	N	0.075	0.154	0.199424873507	gnomAD-4.0.0	6.57497E-06	None	None	None	None	N	None	0	6.55996E-05	None	0	0	None	0	0	0	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
C/A	0.1601	likely_benign	0.1466	benign	-0.813	Destabilizing	0.003	N	0.135	neutral	None	None	None	None	N
C/D	0.2998	likely_benign	0.2637	benign	-0.139	Destabilizing	0.035	N	0.425	neutral	None	None	None	None	N
C/E	0.2501	likely_benign	0.2256	benign	-0.146	Destabilizing	0.007	N	0.257	neutral	None	None	None	None	N
C/F	0.105	likely_benign	0.1012	benign	-0.908	Destabilizing	0.162	N	0.593	neutral	N	0.512753269	None	None	N
C/G	0.0999	likely_benign	0.0844	benign	-0.982	Destabilizing	0.011	N	0.231	neutral	N	0.418016311	None	None	N
C/H	0.1115	likely_benign	0.0985	benign	-1.369	Destabilizing	0.204	N	0.534	neutral	None	None	None	None	N
C/I	0.1625	likely_benign	0.1582	benign	-0.444	Destabilizing	0.068	N	0.485	neutral	None	None	None	None	N
C/K	0.1405	likely_benign	0.1179	benign	-0.074	Destabilizing	None	N	0.078	neutral	None	None	None	None	N
C/L	0.1637	likely_benign	0.1508	benign	-0.444	Destabilizing	0.015	N	0.265	neutral	None	None	None	None	N
C/M	0.2651	likely_benign	0.2599	benign	-0.014	Destabilizing	0.439	N	0.288	neutral	None	None	None	None	N
C/N	0.1855	likely_benign	0.1712	benign	0.145	Stabilizing	0.015	N	0.341	neutral	None	None	None	None	N
C/P	0.8881	likely_pathogenic	0.8524	pathogenic	-0.542	Destabilizing	0.068	N	0.548	neutral	None	None	None	None	N
C/Q	0.1106	likely_benign	0.0981	benign	-0.043	Destabilizing	0.018	N	0.401	neutral	None	None	None	None	N
C/R	0.0587	likely_benign	0.0505	benign	0.074	Stabilizing	None	N	0.075	neutral	N	0.334186993	None	None	N
C/S	0.1207	likely_benign	0.1112	benign	-0.208	Destabilizing	0.011	N	0.292	neutral	N	0.432945691	None	None	N
C/T	0.1559	likely_benign	0.1474	benign	-0.087	Destabilizing	0.015	N	0.237	neutral	None	None	None	None	N
C/V	0.1409	likely_benign	0.1376	benign	-0.542	Destabilizing	0.015	N	0.255	neutral	None	None	None	None	N
C/W	0.2566	likely_benign	0.2269	benign	-0.925	Destabilizing	0.69	D	0.4	neutral	N	0.494938299	None	None	N
C/Y	0.1264	likely_benign	0.1144	benign	-0.739	Destabilizing	0.162	N	0.609	neutral	N	0.494591583	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.