TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32136	96631;96632;96633	chr2:178543567;178543566;178543565	chr2:179408294;179408293;179408292
N2AB	30495	91708;91709;91710	chr2:178543567;178543566;178543565	chr2:179408294;179408293;179408292
N2A	29568	88927;88928;88929	chr2:178543567;178543566;178543565	chr2:179408294;179408293;179408292
N2B	23071	69436;69437;69438	chr2:178543567;178543566;178543565	chr2:179408294;179408293;179408292
Novex-1	23196	69811;69812;69813	chr2:178543567;178543566;178543565	chr2:179408294;179408293;179408292
Novex-2	23263	70012;70013;70014	chr2:178543567;178543566;178543565	chr2:179408294;179408293;179408292
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-122
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.7023
• 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
P/A	None	None	0.98	N	0.551	0.379	0.33085137897	gnomAD-4.0.0	1.37151E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79908E-06	0	0
P/S	rs1553518099	None	0.98	N	0.563	0.413	0.373357554552	gnomAD-4.0.0	5.48604E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.29679E-06	0	1.65782E-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
P/A	0.0811	likely_benign	0.0892	benign	-0.597	Destabilizing	0.98	D	0.551	neutral	N	0.457030485	None	None	I
P/C	0.6333	likely_pathogenic	0.6242	pathogenic	-0.533	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
P/D	0.7274	likely_pathogenic	0.7521	pathogenic	-0.355	Destabilizing	0.985	D	0.541	neutral	None	None	None	None	I
P/E	0.4813	ambiguous	0.5301	ambiguous	-0.464	Destabilizing	0.97	D	0.564	neutral	None	None	None	None	I
P/F	0.632	likely_pathogenic	0.6466	pathogenic	-0.802	Destabilizing	0.996	D	0.701	prob.neutral	None	None	None	None	I
P/G	0.4625	ambiguous	0.4922	ambiguous	-0.758	Destabilizing	0.985	D	0.591	neutral	None	None	None	None	I
P/H	0.3053	likely_benign	0.3026	benign	-0.337	Destabilizing	0.041	N	0.294	neutral	None	None	None	None	I
P/I	0.3274	likely_benign	0.3366	benign	-0.319	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	I
P/K	0.4888	ambiguous	0.496	ambiguous	-0.444	Destabilizing	0.97	D	0.537	neutral	None	None	None	None	I
P/L	0.1454	likely_benign	0.15	benign	-0.319	Destabilizing	0.994	D	0.607	neutral	N	0.478818432	None	None	I
P/M	0.3077	likely_benign	0.3219	benign	-0.244	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	I
P/N	0.4509	ambiguous	0.4736	ambiguous	-0.131	Destabilizing	0.991	D	0.56	neutral	None	None	None	None	I
P/Q	0.2241	likely_benign	0.2418	benign	-0.395	Destabilizing	0.994	D	0.594	neutral	N	0.477297495	None	None	I
P/R	0.3501	ambiguous	0.3489	ambiguous	0.096	Stabilizing	0.989	D	0.609	neutral	N	0.472132934	None	None	I
P/S	0.1817	likely_benign	0.198	benign	-0.523	Destabilizing	0.98	D	0.563	neutral	N	0.482221792	None	None	I
P/T	0.1401	likely_benign	0.1513	benign	-0.529	Destabilizing	0.994	D	0.515	neutral	N	0.471118976	None	None	I
P/V	0.1991	likely_benign	0.2078	benign	-0.375	Destabilizing	0.999	D	0.587	neutral	None	None	None	None	I
P/W	0.8167	likely_pathogenic	0.8187	pathogenic	-0.884	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
P/Y	0.6	likely_pathogenic	0.6122	pathogenic	-0.575	Destabilizing	0.991	D	0.643	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.