TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24570	73933;73934;73935	chr2:178572424;178572423;178572422	chr2:179437151;179437150;179437149
N2AB	22929	69010;69011;69012	chr2:178572424;178572423;178572422	chr2:179437151;179437150;179437149
N2A	22002	66229;66230;66231	chr2:178572424;178572423;178572422	chr2:179437151;179437150;179437149
N2B	15505	46738;46739;46740	chr2:178572424;178572423;178572422	chr2:179437151;179437150;179437149
Novex-1	15630	47113;47114;47115	chr2:178572424;178572423;178572422	chr2:179437151;179437150;179437149
Novex-2	15697	47314;47315;47316	chr2:178572424;178572423;178572422	chr2:179437151;179437150;179437149
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-66
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.0859
• 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/G	None	None	0.006	N	0.433	0.083	0.212008924253	gnomAD-4.0.0	1.59325E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4332E-05	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	0.3053	likely_benign	0.2912	benign	-0.975	Destabilizing	0.001	N	0.325	neutral	None	None	None	None	N
A/D	0.5611	ambiguous	0.4242	ambiguous	-1.513	Destabilizing	0.176	N	0.501	neutral	None	None	None	None	N
A/E	0.5002	ambiguous	0.3879	ambiguous	-1.497	Destabilizing	0.311	N	0.497	neutral	N	0.489908121	None	None	N
A/F	0.4065	ambiguous	0.302	benign	-1.104	Destabilizing	0.849	D	0.532	neutral	None	None	None	None	N
A/G	0.2193	likely_benign	0.178	benign	-1.349	Destabilizing	0.006	N	0.433	neutral	N	0.454584826	None	None	N
A/H	0.5576	ambiguous	0.4631	ambiguous	-1.62	Destabilizing	0.919	D	0.531	neutral	None	None	None	None	N
A/I	0.2209	likely_benign	0.1592	benign	-0.303	Destabilizing	0.444	N	0.471	neutral	None	None	None	None	N
A/K	0.7085	likely_pathogenic	0.5999	pathogenic	-1.253	Destabilizing	0.615	D	0.497	neutral	None	None	None	None	N
A/L	0.1794	likely_benign	0.1415	benign	-0.303	Destabilizing	0.102	N	0.413	neutral	None	None	None	None	N
A/M	0.1877	likely_benign	0.1565	benign	-0.208	Destabilizing	0.248	N	0.378	neutral	None	None	None	None	N
A/N	0.2657	likely_benign	0.1941	benign	-1.066	Destabilizing	None	N	0.331	neutral	None	None	None	None	N
A/P	0.9286	likely_pathogenic	0.8661	pathogenic	-0.503	Destabilizing	0.696	D	0.545	neutral	N	0.493353858	None	None	N
A/Q	0.4635	ambiguous	0.3687	ambiguous	-1.162	Destabilizing	0.919	D	0.533	neutral	None	None	None	None	N
A/R	0.6752	likely_pathogenic	0.5638	ambiguous	-0.979	Destabilizing	0.849	D	0.539	neutral	None	None	None	None	N
A/S	0.0966	likely_benign	0.0849	benign	-1.442	Destabilizing	0.005	N	0.456	neutral	N	0.401097058	None	None	N
A/T	0.0751	likely_benign	0.0683	benign	-1.322	Destabilizing	0.001	N	0.261	neutral	N	0.385551602	None	None	N
A/V	0.1108	likely_benign	0.0862	benign	-0.503	Destabilizing	0.006	N	0.261	neutral	N	0.432822687	None	None	N
A/W	0.8333	likely_pathogenic	0.7626	pathogenic	-1.55	Destabilizing	0.992	D	0.593	neutral	None	None	None	None	N
A/Y	0.5451	ambiguous	0.4651	ambiguous	-1.103	Destabilizing	0.919	D	0.535	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.