TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18228	54907;54908;54909	chr2:178604005;178604004;178604003	chr2:179468732;179468731;179468730
N2AB	16587	49984;49985;49986	chr2:178604005;178604004;178604003	chr2:179468732;179468731;179468730
N2A	15660	47203;47204;47205	chr2:178604005;178604004;178604003	chr2:179468732;179468731;179468730
N2B	9163	27712;27713;27714	chr2:178604005;178604004;178604003	chr2:179468732;179468731;179468730
Novex-1	9288	28087;28088;28089	chr2:178604005;178604004;178604003	chr2:179468732;179468731;179468730
Novex-2	9355	28288;28289;28290	chr2:178604005;178604004;178604003	chr2:179468732;179468731;179468730
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-20
• Domain position: 63
• Structural Position: 88
• Q(SASA): 0.3322
• 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
G/D	rs2154194670	None	0.946	N	0.754	0.369	0.270447802918	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
G/D	rs2154194670	None	0.946	N	0.754	0.369	0.270447802918	gnomAD-4.0.0	6.57592E-06	None	None	None	None	I	None	2.40639E-05	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
G/A	0.247	likely_benign	0.1538	benign	-0.644	Destabilizing	0.035	N	0.302	neutral	N	0.453854107	None	None	I
G/C	0.4776	ambiguous	0.3337	benign	-0.934	Destabilizing	0.993	D	0.739	prob.delet.	N	0.517790942	None	None	I
G/D	0.4319	ambiguous	0.2936	benign	-0.976	Destabilizing	0.946	D	0.754	deleterious	N	0.45856928	None	None	I
G/E	0.4697	ambiguous	0.2861	benign	-1.061	Destabilizing	0.959	D	0.729	prob.delet.	None	None	None	None	I
G/F	0.8391	likely_pathogenic	0.7003	pathogenic	-1.033	Destabilizing	0.994	D	0.755	deleterious	None	None	None	None	I
G/H	0.7483	likely_pathogenic	0.5698	pathogenic	-1.194	Destabilizing	0.998	D	0.717	prob.delet.	None	None	None	None	I
G/I	0.617	likely_pathogenic	0.4216	ambiguous	-0.381	Destabilizing	0.959	D	0.759	deleterious	None	None	None	None	I
G/K	0.8194	likely_pathogenic	0.6538	pathogenic	-1.183	Destabilizing	0.959	D	0.733	prob.delet.	None	None	None	None	I
G/L	0.7346	likely_pathogenic	0.553	ambiguous	-0.381	Destabilizing	0.921	D	0.729	prob.delet.	None	None	None	None	I
G/M	0.7239	likely_pathogenic	0.5336	ambiguous	-0.369	Destabilizing	0.994	D	0.735	prob.delet.	None	None	None	None	I
G/N	0.395	ambiguous	0.2803	benign	-0.821	Destabilizing	0.959	D	0.735	prob.delet.	None	None	None	None	I
G/P	0.9107	likely_pathogenic	0.8481	pathogenic	-0.428	Destabilizing	0.979	D	0.741	deleterious	None	None	None	None	I
G/Q	0.6588	likely_pathogenic	0.468	ambiguous	-1.035	Destabilizing	0.979	D	0.753	deleterious	None	None	None	None	I
G/R	0.7621	likely_pathogenic	0.5722	pathogenic	-0.842	Destabilizing	0.946	D	0.751	deleterious	N	0.472669154	None	None	I
G/S	0.2014	likely_benign	0.1318	benign	-1.062	Destabilizing	0.716	D	0.57	neutral	N	0.454027465	None	None	I
G/T	0.2839	likely_benign	0.1759	benign	-1.07	Destabilizing	0.171	N	0.378	neutral	None	None	None	None	I
G/V	0.4393	ambiguous	0.2694	benign	-0.428	Destabilizing	0.898	D	0.732	prob.delet.	N	0.470575786	None	None	I
G/W	0.7634	likely_pathogenic	0.5831	pathogenic	-1.333	Destabilizing	0.998	D	0.723	prob.delet.	None	None	None	None	I
G/Y	0.709	likely_pathogenic	0.5177	ambiguous	-0.942	Destabilizing	0.998	D	0.751	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.