TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8378	25357;25358;25359	chr2:178717742;178717741;178717740	chr2:179582469;179582468;179582467
N2AB	8061	24406;24407;24408	chr2:178717742;178717741;178717740	chr2:179582469;179582468;179582467
N2A	7134	21625;21626;21627	chr2:178717742;178717741;178717740	chr2:179582469;179582468;179582467
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: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-69
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.2808
• 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
A/V	None	None	0.473	N	0.395	0.25	0.417334834585	gnomAD-4.0.0	1.36897E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99661E-07	1.16069E-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	0.4687	ambiguous	0.5293	ambiguous	-0.782	Destabilizing	0.029	N	0.329	neutral	None	None	None	None	I
A/D	0.3057	likely_benign	0.3892	ambiguous	-0.884	Destabilizing	0.804	D	0.536	neutral	None	None	None	None	I
A/E	0.2613	likely_benign	0.3363	benign	-0.902	Destabilizing	0.813	D	0.47	neutral	N	0.440799957	None	None	I
A/F	0.2757	likely_benign	0.3317	benign	-0.745	Destabilizing	0.964	D	0.551	neutral	None	None	None	None	I
A/G	0.1671	likely_benign	0.2002	benign	-0.884	Destabilizing	0.232	N	0.417	neutral	D	0.523746628	None	None	I
A/H	0.3654	ambiguous	0.4427	ambiguous	-0.872	Destabilizing	0.982	D	0.524	neutral	None	None	None	None	I
A/I	0.1741	likely_benign	0.1978	benign	-0.151	Destabilizing	0.885	D	0.479	neutral	None	None	None	None	I
A/K	0.3497	ambiguous	0.4532	ambiguous	-1.006	Destabilizing	0.08	N	0.307	neutral	None	None	None	None	I
A/L	0.1505	likely_benign	0.1761	benign	-0.151	Destabilizing	0.046	N	0.315	neutral	None	None	None	None	I
A/M	0.2002	likely_benign	0.2261	benign	-0.32	Destabilizing	0.982	D	0.499	neutral	None	None	None	None	I
A/N	0.2187	likely_benign	0.2517	benign	-0.817	Destabilizing	0.325	N	0.557	neutral	None	None	None	None	I
A/P	0.5645	likely_pathogenic	0.6861	pathogenic	-0.275	Destabilizing	0.957	D	0.531	neutral	N	0.486719968	None	None	I
A/Q	0.291	likely_benign	0.357	ambiguous	-0.93	Destabilizing	0.982	D	0.531	neutral	None	None	None	None	I
A/R	0.2884	likely_benign	0.3851	ambiguous	-0.66	Destabilizing	0.046	N	0.367	neutral	None	None	None	None	I
A/S	0.0903	likely_benign	0.0952	benign	-1.131	Destabilizing	0.045	N	0.417	neutral	N	0.451075666	None	None	I
A/T	0.0742	likely_benign	0.0745	benign	-1.043	Destabilizing	0.011	N	0.241	neutral	N	0.372596239	None	None	I
A/V	0.1007	likely_benign	0.1138	benign	-0.275	Destabilizing	0.473	N	0.395	neutral	N	0.408210323	None	None	I
A/W	0.6495	likely_pathogenic	0.7508	pathogenic	-1.074	Destabilizing	0.998	D	0.56	neutral	None	None	None	None	I
A/Y	0.3769	ambiguous	0.4443	ambiguous	-0.645	Destabilizing	0.323	N	0.444	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.