TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18544	55855;55856;55857	chr2:178601367;178601366;178601365	chr2:179466094;179466093;179466092
N2AB	16903	50932;50933;50934	chr2:178601367;178601366;178601365	chr2:179466094;179466093;179466092
N2A	15976	48151;48152;48153	chr2:178601367;178601366;178601365	chr2:179466094;179466093;179466092
N2B	9479	28660;28661;28662	chr2:178601367;178601366;178601365	chr2:179466094;179466093;179466092
Novex-1	9604	29035;29036;29037	chr2:178601367;178601366;178601365	chr2:179466094;179466093;179466092
Novex-2	9671	29236;29237;29238	chr2:178601367;178601366;178601365	chr2:179466094;179466093;179466092
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-22
• Domain position: 66
• Structural Position: 98
• Q(SASA): 0.6628
• 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
L/P	None	None	0.859	N	0.644	0.464	0.713293215259	gnomAD-4.0.0	4.78141E-06	None	None	None	None	N	None	0	0	None	0	8.36353E-05	None	0	0	0	0	0
L/V	rs924109444	None	0.004	N	0.138	0.074	0.19670166235	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	3.28947E-03	0	0	None	0	0	0	0	0
L/V	rs924109444	None	0.004	N	0.138	0.074	0.19670166235	gnomAD-4.0.0	1.97384E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	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
L/A	0.268	likely_benign	0.2355	benign	-1.08	Destabilizing	0.272	N	0.525	neutral	None	None	None	None	N
L/C	0.5567	ambiguous	0.46	ambiguous	-0.896	Destabilizing	0.968	D	0.593	neutral	None	None	None	None	N
L/D	0.7521	likely_pathogenic	0.6476	pathogenic	0.079	Stabilizing	0.726	D	0.634	neutral	None	None	None	None	N
L/E	0.4626	ambiguous	0.3745	ambiguous	0.06	Stabilizing	0.726	D	0.643	neutral	None	None	None	None	N
L/F	0.1775	likely_benign	0.1367	benign	-0.752	Destabilizing	0.497	N	0.505	neutral	N	0.499087751	None	None	N
L/G	0.5584	ambiguous	0.4942	ambiguous	-1.34	Destabilizing	0.726	D	0.637	neutral	None	None	None	None	N
L/H	0.2877	likely_benign	0.2185	benign	-0.423	Destabilizing	0.958	D	0.653	neutral	N	0.51167026	None	None	N
L/I	0.0668	likely_benign	0.0624	benign	-0.475	Destabilizing	None	N	0.097	neutral	N	0.429881169	None	None	N
L/K	0.3174	likely_benign	0.2698	benign	-0.484	Destabilizing	0.726	D	0.611	neutral	None	None	None	None	N
L/M	0.1182	likely_benign	0.108	benign	-0.557	Destabilizing	0.567	D	0.546	neutral	None	None	None	None	N
L/N	0.3223	likely_benign	0.2805	benign	-0.356	Destabilizing	0.89	D	0.644	neutral	None	None	None	None	N
L/P	0.5585	ambiguous	0.4681	ambiguous	-0.643	Destabilizing	0.859	D	0.644	neutral	N	0.519481666	None	None	N
L/Q	0.1887	likely_benign	0.1517	benign	-0.48	Destabilizing	0.89	D	0.613	neutral	None	None	None	None	N
L/R	0.2902	likely_benign	0.2189	benign	0.007	Stabilizing	0.667	D	0.618	neutral	N	0.462201445	None	None	N
L/S	0.3374	likely_benign	0.2844	benign	-1.023	Destabilizing	0.726	D	0.535	neutral	None	None	None	None	N
L/T	0.2451	likely_benign	0.2158	benign	-0.91	Destabilizing	0.272	N	0.527	neutral	None	None	None	None	N
L/V	0.0971	likely_benign	0.0839	benign	-0.643	Destabilizing	0.004	N	0.138	neutral	N	0.456123621	None	None	N
L/W	0.4344	ambiguous	0.3198	benign	-0.738	Destabilizing	0.968	D	0.685	prob.neutral	None	None	None	None	N
L/Y	0.3977	ambiguous	0.3142	benign	-0.507	Destabilizing	0.726	D	0.576	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.