TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26571	79936;79937;79938	chr2:178566421;178566420;178566419	chr2:179431148;179431147;179431146
N2AB	24930	75013;75014;75015	chr2:178566421;178566420;178566419	chr2:179431148;179431147;179431146
N2A	24003	72232;72233;72234	chr2:178566421;178566420;178566419	chr2:179431148;179431147;179431146
N2B	17506	52741;52742;52743	chr2:178566421;178566420;178566419	chr2:179431148;179431147;179431146
Novex-1	17631	53116;53117;53118	chr2:178566421;178566420;178566419	chr2:179431148;179431147;179431146
Novex-2	17698	53317;53318;53319	chr2:178566421;178566420;178566419	chr2:179431148;179431147;179431146
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Fn3-81
• Domain position: 85
• Structural Position: 117
• Q(SASA): 0.3537
• 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
L/F	rs879058004	None	0.81	N	0.587	0.176	0.378148810121	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/F	rs879058004	None	0.81	N	0.587	0.176	0.378148810121	gnomAD-4.0.0	3.8447E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	7.18074E-06	0	0
L/I	None	None	0.002	N	0.216	0.028	0.162503812791	gnomAD-4.0.0	4.80129E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.25001E-06	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	0.1269	likely_benign	0.1503	benign	-0.831	Destabilizing	0.25	N	0.519	neutral	None	None	None	None	I
L/C	0.3626	ambiguous	0.3946	ambiguous	-0.763	Destabilizing	0.992	D	0.594	neutral	None	None	None	None	I
L/D	0.5289	ambiguous	0.6183	pathogenic	0.145	Stabilizing	0.447	N	0.62	neutral	None	None	None	None	I
L/E	0.2537	likely_benign	0.2919	benign	0.091	Stabilizing	0.005	N	0.548	neutral	None	None	None	None	I
L/F	0.1051	likely_benign	0.114	benign	-0.607	Destabilizing	0.81	D	0.587	neutral	N	0.449101648	None	None	I
L/G	0.3968	ambiguous	0.4657	ambiguous	-1.048	Destabilizing	0.617	D	0.621	neutral	None	None	None	None	I
L/H	0.2048	likely_benign	0.2228	benign	-0.163	Destabilizing	0.977	D	0.631	neutral	None	None	None	None	I
L/I	0.0731	likely_benign	0.0679	benign	-0.363	Destabilizing	0.002	N	0.216	neutral	N	0.419394817	None	None	I
L/K	0.2101	likely_benign	0.2315	benign	-0.382	Destabilizing	0.447	N	0.62	neutral	None	None	None	None	I
L/M	0.0889	likely_benign	0.0905	benign	-0.432	Destabilizing	0.85	D	0.607	neutral	None	None	None	None	I
L/N	0.2967	likely_benign	0.3506	ambiguous	-0.198	Destabilizing	0.85	D	0.639	neutral	None	None	None	None	I
L/P	0.1348	likely_benign	0.16	benign	-0.485	Destabilizing	0.92	D	0.635	neutral	None	None	None	None	I
L/Q	0.1359	likely_benign	0.1534	benign	-0.372	Destabilizing	0.739	D	0.632	neutral	None	None	None	None	I
L/R	0.1586	likely_benign	0.1764	benign	0.149	Stabilizing	0.85	D	0.633	neutral	None	None	None	None	I
L/S	0.1888	likely_benign	0.2212	benign	-0.811	Destabilizing	0.549	D	0.589	neutral	N	0.462588234	None	None	I
L/T	0.1213	likely_benign	0.1343	benign	-0.744	Destabilizing	0.617	D	0.492	neutral	None	None	None	None	I
L/V	0.0709	likely_benign	0.0693	benign	-0.485	Destabilizing	0.001	N	0.216	neutral	N	0.3672352	None	None	I
L/W	0.2008	likely_benign	0.2374	benign	-0.587	Destabilizing	0.992	D	0.641	neutral	None	None	None	None	I
L/Y	0.274	likely_benign	0.3016	benign	-0.356	Destabilizing	0.92	D	0.621	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.