TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24931	75016;75017;75018	chr2:178571341;178571340;178571339	chr2:179436068;179436067;179436066
N2AB	23290	70093;70094;70095	chr2:178571341;178571340;178571339	chr2:179436068;179436067;179436066
N2A	22363	67312;67313;67314	chr2:178571341;178571340;178571339	chr2:179436068;179436067;179436066
N2B	15866	47821;47822;47823	chr2:178571341;178571340;178571339	chr2:179436068;179436067;179436066
Novex-1	15991	48196;48197;48198	chr2:178571341;178571340;178571339	chr2:179436068;179436067;179436066
Novex-2	16058	48397;48398;48399	chr2:178571341;178571340;178571339	chr2:179436068;179436067;179436066
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-69
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.5564
• 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
E/D	rs1314632891	-0.815	0.472	N	0.475	0.059	0.183819452728	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	1.14784E-04	0	None	0	0	None	0	None	0	0	0
E/D	rs1314632891	-0.815	0.472	N	0.475	0.059	0.183819452728	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
E/D	rs1314632891	-0.815	0.472	N	0.475	0.059	0.183819452728	gnomAD-4.0.0	1.31532E-05	None	None	None	None	I	None	4.82742E-05	0	None	0	0	None	0	0	0	0	0
E/K	rs369679134	0.018	0.012	N	0.147	0.205	None	gnomAD-2.1.1	1.07E-05	None	None	None	None	I	None	0	0	None	0	5.14E-05	None	0	None	0	1.57E-05	0
E/K	rs369679134	0.018	0.012	N	0.147	0.205	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	0	0	0	2.88351E-04	1.94024E-04	None	0	0	1.47E-05	0	0
E/K	rs369679134	0.018	0.012	N	0.147	0.205	None	gnomAD-4.0.0	1.36366E-05	None	None	None	None	I	None	0	0	None	6.7595E-05	2.23174E-05	None	0	0	1.52595E-05	0	1.60174E-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
E/A	0.1567	likely_benign	0.1487	benign	-0.241	Destabilizing	0.309	N	0.412	neutral	N	0.424952565	None	None	I
E/C	0.8481	likely_pathogenic	0.8299	pathogenic	-0.298	Destabilizing	0.996	D	0.601	neutral	None	None	None	None	I
E/D	0.247	likely_benign	0.259	benign	-0.756	Destabilizing	0.472	N	0.475	neutral	N	0.515614642	None	None	I
E/F	0.8191	likely_pathogenic	0.801	pathogenic	0.333	Stabilizing	0.984	D	0.588	neutral	None	None	None	None	I
E/G	0.3157	likely_benign	0.3157	benign	-0.541	Destabilizing	0.003	N	0.362	neutral	N	0.496508806	None	None	I
E/H	0.6067	likely_pathogenic	0.5843	pathogenic	0.568	Stabilizing	0.984	D	0.555	neutral	None	None	None	None	I
E/I	0.2694	likely_benign	0.2487	benign	0.551	Stabilizing	0.91	D	0.602	neutral	None	None	None	None	I
E/K	0.1379	likely_benign	0.132	benign	0.137	Stabilizing	0.012	N	0.147	neutral	N	0.439788732	None	None	I
E/L	0.3767	ambiguous	0.3617	ambiguous	0.551	Stabilizing	0.742	D	0.559	neutral	None	None	None	None	I
E/M	0.4211	ambiguous	0.3918	ambiguous	0.478	Stabilizing	0.996	D	0.574	neutral	None	None	None	None	I
E/N	0.4323	ambiguous	0.4429	ambiguous	-0.475	Destabilizing	0.742	D	0.491	neutral	None	None	None	None	I
E/P	0.3594	ambiguous	0.3183	benign	0.309	Stabilizing	0.984	D	0.592	neutral	None	None	None	None	I
E/Q	0.1617	likely_benign	0.1516	benign	-0.331	Destabilizing	0.684	D	0.496	neutral	N	0.484657017	None	None	I
E/R	0.2751	likely_benign	0.2496	benign	0.523	Stabilizing	0.59	D	0.481	neutral	None	None	None	None	I
E/S	0.3015	likely_benign	0.2911	benign	-0.656	Destabilizing	0.373	N	0.488	neutral	None	None	None	None	I
E/T	0.2643	likely_benign	0.2589	benign	-0.387	Destabilizing	0.037	N	0.275	neutral	None	None	None	None	I
E/V	0.1702	likely_benign	0.1618	benign	0.309	Stabilizing	0.684	D	0.549	neutral	N	0.480443276	None	None	I
E/W	0.9567	likely_pathogenic	0.9494	pathogenic	0.562	Stabilizing	0.996	D	0.619	neutral	None	None	None	None	I
E/Y	0.7141	likely_pathogenic	0.6964	pathogenic	0.614	Stabilizing	0.984	D	0.586	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.