TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18149	54670;54671;54672	chr2:178604242;178604241;178604240	chr2:179468969;179468968;179468967
N2AB	16508	49747;49748;49749	chr2:178604242;178604241;178604240	chr2:179468969;179468968;179468967
N2A	15581	46966;46967;46968	chr2:178604242;178604241;178604240	chr2:179468969;179468968;179468967
N2B	9084	27475;27476;27477	chr2:178604242;178604241;178604240	chr2:179468969;179468968;179468967
Novex-1	9209	27850;27851;27852	chr2:178604242;178604241;178604240	chr2:179468969;179468968;179468967
Novex-2	9276	28051;28052;28053	chr2:178604242;178604241;178604240	chr2:179468969;179468968;179468967
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-19
• Domain position: 85
• Structural Position: 117
• Q(SASA): 0.3972
• 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
I/N	None	None	0.055	N	0.599	0.121	0.342400092842	gnomAD-4.0.0	1.65667E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.52073E-05	0
I/V	None	None	0.005	N	0.267	0.056	0.349429436713	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-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
I/A	0.2146	likely_benign	0.1862	benign	-1.587	Destabilizing	None	N	0.317	neutral	None	None	None	None	I
I/C	0.5327	ambiguous	0.4635	ambiguous	-1.028	Destabilizing	0.356	N	0.565	neutral	None	None	None	None	I
I/D	0.517	ambiguous	0.4021	ambiguous	-0.815	Destabilizing	0.072	N	0.592	neutral	None	None	None	None	I
I/E	0.3524	ambiguous	0.2824	benign	-0.843	Destabilizing	0.072	N	0.558	neutral	None	None	None	None	I
I/F	0.1489	likely_benign	0.1079	benign	-1.171	Destabilizing	0.295	N	0.54	neutral	N	0.465759697	None	None	I
I/G	0.5197	ambiguous	0.442	ambiguous	-1.868	Destabilizing	0.038	N	0.565	neutral	None	None	None	None	I
I/H	0.4147	ambiguous	0.3173	benign	-0.907	Destabilizing	0.628	D	0.598	neutral	None	None	None	None	I
I/K	0.2804	likely_benign	0.2206	benign	-0.959	Destabilizing	None	N	0.463	neutral	None	None	None	None	I
I/L	0.106	likely_benign	0.0941	benign	-0.908	Destabilizing	0.005	N	0.268	neutral	N	0.45983593	None	None	I
I/M	0.1037	likely_benign	0.0978	benign	-0.724	Destabilizing	0.295	N	0.565	neutral	N	0.471093074	None	None	I
I/N	0.2009	likely_benign	0.1565	benign	-0.75	Destabilizing	0.055	N	0.599	neutral	N	0.479595127	None	None	I
I/P	0.4669	ambiguous	0.381	ambiguous	-1.102	Destabilizing	0.136	N	0.591	neutral	None	None	None	None	I
I/Q	0.2955	likely_benign	0.2466	benign	-0.991	Destabilizing	0.214	N	0.598	neutral	None	None	None	None	I
I/R	0.2705	likely_benign	0.2084	benign	-0.292	Destabilizing	0.038	N	0.559	neutral	None	None	None	None	I
I/S	0.2046	likely_benign	0.1701	benign	-1.39	Destabilizing	0.012	N	0.567	neutral	N	0.481461996	None	None	I
I/T	0.1239	likely_benign	0.1025	benign	-1.305	Destabilizing	None	N	0.333	neutral	N	0.471765077	None	None	I
I/V	0.0653	likely_benign	0.0653	benign	-1.102	Destabilizing	0.005	N	0.267	neutral	N	0.454526111	None	None	I
I/W	0.7217	likely_pathogenic	0.6086	pathogenic	-1.131	Destabilizing	0.864	D	0.617	neutral	None	None	None	None	I
I/Y	0.3944	ambiguous	0.3104	benign	-0.937	Destabilizing	0.356	N	0.575	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.