TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23856	71791;71792;71793	chr2:178574566;178574565;178574564	chr2:179439293;179439292;179439291
N2AB	22215	66868;66869;66870	chr2:178574566;178574565;178574564	chr2:179439293;179439292;179439291
N2A	21288	64087;64088;64089	chr2:178574566;178574565;178574564	chr2:179439293;179439292;179439291
N2B	14791	44596;44597;44598	chr2:178574566;178574565;178574564	chr2:179439293;179439292;179439291
Novex-1	14916	44971;44972;44973	chr2:178574566;178574565;178574564	chr2:179439293;179439292;179439291
Novex-2	14983	45172;45173;45174	chr2:178574566;178574565;178574564	chr2:179439293;179439292;179439291
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-61
• Domain position: 31
• Structural Position: 33
• Q(SASA): 0.2343
• 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
S/R	rs1060500519	None	1.0	N	0.791	0.542	0.375861065471	gnomAD-4.0.0	6.84309E-07	None	None	None	None	I	None	0	0	None	0	2.5222E-05	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
S/A	0.2586	likely_benign	0.262	benign	-0.472	Destabilizing	0.998	D	0.595	neutral	None	None	None	None	I
S/C	0.1738	likely_benign	0.1633	benign	-0.301	Destabilizing	1.0	D	0.759	deleterious	N	0.499200411	None	None	I
S/D	0.8921	likely_pathogenic	0.9416	pathogenic	-0.501	Destabilizing	0.999	D	0.742	deleterious	None	None	None	None	I
S/E	0.9296	likely_pathogenic	0.9569	pathogenic	-0.555	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	I
S/F	0.5531	ambiguous	0.6296	pathogenic	-0.879	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
S/G	0.3708	ambiguous	0.3893	ambiguous	-0.66	Destabilizing	0.999	D	0.587	neutral	N	0.476414305	None	None	I
S/H	0.6178	likely_pathogenic	0.7079	pathogenic	-1.261	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	I
S/I	0.578	likely_pathogenic	0.6962	pathogenic	-0.092	Destabilizing	1.0	D	0.817	deleterious	N	0.518176812	None	None	I
S/K	0.9535	likely_pathogenic	0.9781	pathogenic	-0.707	Destabilizing	0.999	D	0.728	prob.delet.	None	None	None	None	I
S/L	0.251	likely_benign	0.333	benign	-0.092	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	I
S/M	0.4125	ambiguous	0.5002	ambiguous	0.349	Stabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
S/N	0.3847	ambiguous	0.5017	ambiguous	-0.561	Destabilizing	0.999	D	0.72	prob.delet.	N	0.505668418	None	None	I
S/P	0.9869	likely_pathogenic	0.9901	pathogenic	-0.187	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
S/Q	0.8214	likely_pathogenic	0.8799	pathogenic	-0.832	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
S/R	0.9374	likely_pathogenic	0.964	pathogenic	-0.485	Destabilizing	1.0	D	0.791	deleterious	N	0.497386305	None	None	I
S/T	0.2406	likely_benign	0.3222	benign	-0.561	Destabilizing	0.999	D	0.598	neutral	N	0.479081467	None	None	I
S/V	0.5323	ambiguous	0.6169	pathogenic	-0.187	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	I
S/W	0.7528	likely_pathogenic	0.8033	pathogenic	-0.878	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
S/Y	0.479	ambiguous	0.5682	pathogenic	-0.605	Destabilizing	1.0	D	0.822	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.