TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4841	14746;14747;14748	chr2:178735925;178735924;178735923	chr2:179600652;179600651;179600650
N2AB	4524	13795;13796;13797	chr2:178735925;178735924;178735923	chr2:179600652;179600651;179600650
N2A	3597	11014;11015;11016	chr2:178735925;178735924;178735923	chr2:179600652;179600651;179600650
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: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Ig-31
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.2638
• 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
W/R	rs2081362230	None	None	N	0.363	0.24	0.0762999501168	gnomAD-4.0.0	1.36836E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79889E-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
W/A	0.1041	likely_benign	0.1014	benign	-3.055	Highly Destabilizing	None	N	0.364	neutral	None	None	None	None	I
W/C	0.0701	likely_benign	0.0698	benign	-1.881	Destabilizing	None	N	0.291	neutral	D	0.568557587	None	None	I
W/D	0.2648	likely_benign	0.2021	benign	-2.118	Highly Destabilizing	None	N	0.373	neutral	None	None	None	None	I
W/E	0.1622	likely_benign	0.1443	benign	-2.012	Highly Destabilizing	None	N	0.367	neutral	None	None	None	None	I
W/F	0.0876	likely_benign	0.0771	benign	-1.84	Destabilizing	None	N	0.152	neutral	None	None	None	None	I
W/G	0.0658	likely_benign	0.0577	benign	-3.298	Highly Destabilizing	None	N	0.294	neutral	D	0.552874491	None	None	I
W/H	0.064	likely_benign	0.0577	benign	-1.908	Destabilizing	None	N	0.291	neutral	None	None	None	None	I
W/I	0.0959	likely_benign	0.095	benign	-2.165	Highly Destabilizing	None	N	0.367	neutral	None	None	None	None	I
W/K	0.0924	likely_benign	0.0863	benign	-2.193	Highly Destabilizing	None	N	0.366	neutral	None	None	None	None	I
W/L	0.0741	likely_benign	0.0731	benign	-2.165	Highly Destabilizing	None	N	0.291	neutral	N	0.49432933	None	None	I
W/M	0.1647	likely_benign	0.1619	benign	-1.764	Destabilizing	None	N	0.234	neutral	None	None	None	None	I
W/N	0.1714	likely_benign	0.1348	benign	-2.674	Highly Destabilizing	None	N	0.371	neutral	None	None	None	None	I
W/P	0.592	likely_pathogenic	0.4825	ambiguous	-2.484	Highly Destabilizing	None	N	0.396	neutral	None	None	None	None	I
W/Q	0.0755	likely_benign	0.0691	benign	-2.538	Highly Destabilizing	None	N	0.302	neutral	None	None	None	None	I
W/R	0.0526	likely_benign	0.0507	benign	-1.802	Destabilizing	None	N	0.363	neutral	N	0.507623594	None	None	I
W/S	0.1023	likely_benign	0.0876	benign	-3.073	Highly Destabilizing	None	N	0.367	neutral	N	0.499760562	None	None	I
W/T	0.0862	likely_benign	0.0874	benign	-2.911	Highly Destabilizing	None	N	0.294	neutral	None	None	None	None	I
W/V	0.0878	likely_benign	0.0899	benign	-2.484	Highly Destabilizing	None	N	0.365	neutral	None	None	None	None	I
W/Y	0.0876	likely_benign	0.077	benign	-1.741	Destabilizing	None	N	0.152	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.