TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21261	64006;64007;64008	chr2:178587528;178587527;178587526	chr2:179452255;179452254;179452253
N2AB	19620	59083;59084;59085	chr2:178587528;178587527;178587526	chr2:179452255;179452254;179452253
N2A	18693	56302;56303;56304	chr2:178587528;178587527;178587526	chr2:179452255;179452254;179452253
N2B	12196	36811;36812;36813	chr2:178587528;178587527;178587526	chr2:179452255;179452254;179452253
Novex-1	12321	37186;37187;37188	chr2:178587528;178587527;178587526	chr2:179452255;179452254;179452253
Novex-2	12388	37387;37388;37389	chr2:178587528;178587527;178587526	chr2:179452255;179452254;179452253
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-123
• Domain position: 85
• Structural Position: 174
• Q(SASA): 0.1242
• 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
V/I	None	None	0.997	N	0.551	0.321	0.555788435936	gnomAD-4.0.0	3.20566E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.88667E-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
V/A	0.9302	likely_pathogenic	0.9385	pathogenic	-2.257	Highly Destabilizing	0.999	D	0.64	neutral	D	0.523939441	None	None	I
V/C	0.9499	likely_pathogenic	0.9615	pathogenic	-1.809	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
V/D	0.9991	likely_pathogenic	0.9989	pathogenic	-3.039	Highly Destabilizing	1.0	D	0.871	deleterious	D	0.535802725	None	None	I
V/E	0.9972	likely_pathogenic	0.9967	pathogenic	-2.793	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	I
V/F	0.9515	likely_pathogenic	0.9519	pathogenic	-1.373	Destabilizing	1.0	D	0.836	deleterious	D	0.523178972	None	None	I
V/G	0.9633	likely_pathogenic	0.9622	pathogenic	-2.827	Highly Destabilizing	1.0	D	0.869	deleterious	D	0.535802725	None	None	I
V/H	0.9989	likely_pathogenic	0.9989	pathogenic	-2.677	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	I
V/I	0.1675	likely_benign	0.1764	benign	-0.649	Destabilizing	0.997	D	0.551	neutral	N	0.480952847	None	None	I
V/K	0.9975	likely_pathogenic	0.9971	pathogenic	-1.986	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	I
V/L	0.84	likely_pathogenic	0.8586	pathogenic	-0.649	Destabilizing	0.997	D	0.659	neutral	N	0.489112247	None	None	I
V/M	0.8933	likely_pathogenic	0.9043	pathogenic	-0.689	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
V/N	0.9964	likely_pathogenic	0.9961	pathogenic	-2.401	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	I
V/P	0.9968	likely_pathogenic	0.9964	pathogenic	-1.159	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	I
V/Q	0.9964	likely_pathogenic	0.9961	pathogenic	-2.187	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	I
V/R	0.9943	likely_pathogenic	0.9932	pathogenic	-1.847	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	I
V/S	0.9841	likely_pathogenic	0.9849	pathogenic	-3.001	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	I
V/T	0.9189	likely_pathogenic	0.9293	pathogenic	-2.606	Highly Destabilizing	0.999	D	0.674	neutral	None	None	None	None	I
V/W	0.9994	likely_pathogenic	0.9994	pathogenic	-1.976	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I
V/Y	0.996	likely_pathogenic	0.9959	pathogenic	-1.591	Destabilizing	1.0	D	0.829	deleterious	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.