TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29103	87532;87533;87534	chr2:178558047;178558046;178558045	chr2:179422774;179422773;179422772
N2AB	27462	82609;82610;82611	chr2:178558047;178558046;178558045	chr2:179422774;179422773;179422772
N2A	26535	79828;79829;79830	chr2:178558047;178558046;178558045	chr2:179422774;179422773;179422772
N2B	20038	60337;60338;60339	chr2:178558047;178558046;178558045	chr2:179422774;179422773;179422772
Novex-1	20163	60712;60713;60714	chr2:178558047;178558046;178558045	chr2:179422774;179422773;179422772
Novex-2	20230	60913;60914;60915	chr2:178558047;178558046;178558045	chr2:179422774;179422773;179422772
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: Ig-145
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.3618
• 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	rs375374455	-0.86	0.514	N	0.526	0.178	None	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	1.29149E-04	0	None	0	0	None	0	None	0	0	0
N/S	rs375374455	-0.86	0.514	N	0.526	0.178	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
N/S	rs375374455	-0.86	0.514	N	0.526	0.178	None	gnomAD-4.0.0	4.33748E-06	None	None	None	None	N	None	5.33803E-05	0	None	0	0	None	0	0	1.69511E-06	0	1.60087E-05

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	0.1981	likely_benign	0.1902	benign	-0.909	Destabilizing	0.737	D	0.485	neutral	None	None	None	None	N
N/C	0.1495	likely_benign	0.1394	benign	-0.453	Destabilizing	0.998	D	0.592	neutral	None	None	None	None	N
N/D	0.2515	likely_benign	0.2358	benign	-1.779	Destabilizing	0.912	D	0.503	neutral	N	0.438301157	None	None	N
N/E	0.5204	ambiguous	0.477	ambiguous	-1.583	Destabilizing	0.932	D	0.475	neutral	None	None	None	None	N
N/F	0.2879	likely_benign	0.2928	benign	-0.542	Destabilizing	0.773	D	0.583	neutral	None	None	None	None	N
N/G	0.3233	likely_benign	0.3077	benign	-1.293	Destabilizing	0.932	D	0.494	neutral	None	None	None	None	N
N/H	0.0719	likely_benign	0.0676	benign	-0.945	Destabilizing	0.947	D	0.547	neutral	N	0.424563855	None	None	N
N/I	0.1043	likely_benign	0.1042	benign	0.096	Stabilizing	0.064	N	0.506	neutral	N	0.373076242	None	None	N
N/K	0.4146	ambiguous	0.3691	ambiguous	-0.331	Destabilizing	0.912	D	0.463	neutral	N	0.395953102	None	None	N
N/L	0.137	likely_benign	0.1341	benign	0.096	Stabilizing	0.584	D	0.48	neutral	None	None	None	None	N
N/M	0.215	likely_benign	0.2146	benign	0.381	Stabilizing	0.98	D	0.573	neutral	None	None	None	None	N
N/P	0.9097	likely_pathogenic	0.8605	pathogenic	-0.21	Destabilizing	0.993	D	0.582	neutral	None	None	None	None	N
N/Q	0.3273	likely_benign	0.3018	benign	-1.084	Destabilizing	0.993	D	0.521	neutral	None	None	None	None	N
N/R	0.3998	ambiguous	0.3473	ambiguous	-0.467	Destabilizing	0.98	D	0.519	neutral	None	None	None	None	N
N/S	0.0733	likely_benign	0.0777	benign	-1.236	Destabilizing	0.514	D	0.526	neutral	N	0.40797825	None	None	N
N/T	0.0845	likely_benign	0.083	benign	-0.853	Destabilizing	0.064	N	0.23	neutral	N	0.389234986	None	None	N
N/V	0.1318	likely_benign	0.128	benign	-0.21	Destabilizing	0.083	N	0.526	neutral	None	None	None	None	N
N/W	0.6493	likely_pathogenic	0.6186	pathogenic	-0.435	Destabilizing	0.995	D	0.598	neutral	None	None	None	None	N
N/Y	0.111	likely_benign	0.1059	benign	-0.091	Destabilizing	0.064	N	0.487	neutral	N	0.393491587	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.