TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32939	99040;99041;99042	chr2:178539120;178539119;178539118	chr2:179403847;179403846;179403845
N2AB	31298	94117;94118;94119	chr2:178539120;178539119;178539118	chr2:179403847;179403846;179403845
N2A	30371	91336;91337;91338	chr2:178539120;178539119;178539118	chr2:179403847;179403846;179403845
N2B	23874	71845;71846;71847	chr2:178539120;178539119;178539118	chr2:179403847;179403846;179403845
Novex-1	23999	72220;72221;72222	chr2:178539120;178539119;178539118	chr2:179403847;179403846;179403845
Novex-2	24066	72421;72422;72423	chr2:178539120;178539119;178539118	chr2:179403847;179403846;179403845
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-128
• Domain position: 44
• Structural Position: 50
• Q(SASA): 0.5486
• Predicted PPI site: N

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
T/I	rs1559083229	None	0.051	N	0.305	0.184	0.26169431596	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
T/I	rs1559083229	None	0.051	N	0.305	0.184	0.26169431596	gnomAD-4.0.0	2.73686E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69847E-06	1.15931E-05	0
T/R	None	None	0.934	N	0.365	0.306	0.471211772063	gnomAD-4.0.0	6.84215E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99489E-07	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
T/A	0.0806	likely_benign	0.0749	benign	-0.888	Destabilizing	0.454	N	0.218	neutral	N	0.381337861	None	None	N
T/C	0.3784	ambiguous	0.3022	benign	-0.611	Destabilizing	0.998	D	0.339	neutral	None	None	None	None	N
T/D	0.4576	ambiguous	0.4245	ambiguous	-0.582	Destabilizing	0.842	D	0.342	neutral	None	None	None	None	N
T/E	0.3841	ambiguous	0.3405	ambiguous	-0.579	Destabilizing	0.842	D	0.352	neutral	None	None	None	None	N
T/F	0.2809	likely_benign	0.2261	benign	-0.933	Destabilizing	0.974	D	0.459	neutral	None	None	None	None	N
T/G	0.2456	likely_benign	0.2052	benign	-1.147	Destabilizing	0.728	D	0.428	neutral	None	None	None	None	N
T/H	0.3355	likely_benign	0.2817	benign	-1.391	Destabilizing	0.998	D	0.438	neutral	None	None	None	None	N
T/I	0.1177	likely_benign	0.1006	benign	-0.287	Destabilizing	0.051	N	0.305	neutral	N	0.428707733	None	None	N
T/K	0.2436	likely_benign	0.2062	benign	-0.834	Destabilizing	0.801	D	0.353	neutral	N	0.360711873	None	None	N
T/L	0.087	likely_benign	0.0758	benign	-0.287	Destabilizing	0.525	D	0.354	neutral	None	None	None	None	N
T/M	0.0837	likely_benign	0.0754	benign	0.066	Stabilizing	0.974	D	0.349	neutral	None	None	None	None	N
T/N	0.1165	likely_benign	0.1055	benign	-0.815	Destabilizing	0.842	D	0.269	neutral	None	None	None	None	N
T/P	0.1538	likely_benign	0.1642	benign	-0.456	Destabilizing	0.966	D	0.353	neutral	N	0.409217896	None	None	N
T/Q	0.2742	likely_benign	0.2334	benign	-1.034	Destabilizing	0.974	D	0.353	neutral	None	None	None	None	N
T/R	0.2279	likely_benign	0.2021	benign	-0.521	Destabilizing	0.934	D	0.365	neutral	N	0.446485418	None	None	N
T/S	0.122	likely_benign	0.1067	benign	-1.076	Destabilizing	0.022	N	0.173	neutral	N	0.413834281	None	None	N
T/V	0.1034	likely_benign	0.0886	benign	-0.456	Destabilizing	0.029	N	0.177	neutral	None	None	None	None	N
T/W	0.6958	likely_pathogenic	0.6305	pathogenic	-0.849	Destabilizing	0.998	D	0.492	neutral	None	None	None	None	N
T/Y	0.3442	ambiguous	0.278	benign	-0.626	Destabilizing	0.991	D	0.451	neutral	None	None	None	None	N

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.