TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20067	60424;60425;60426	chr2:178591620;178591619;178591618	chr2:179456347;179456346;179456345
N2AB	18426	55501;55502;55503	chr2:178591620;178591619;178591618	chr2:179456347;179456346;179456345
N2A	17499	52720;52721;52722	chr2:178591620;178591619;178591618	chr2:179456347;179456346;179456345
N2B	11002	33229;33230;33231	chr2:178591620;178591619;178591618	chr2:179456347;179456346;179456345
Novex-1	11127	33604;33605;33606	chr2:178591620;178591619;178591618	chr2:179456347;179456346;179456345
Novex-2	11194	33805;33806;33807	chr2:178591620;178591619;178591618	chr2:179456347;179456346;179456345
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-33
• Domain position: 91
• Structural Position: 127
• Q(SASA): 0.1225
• 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
I/T	rs373690962	-2.826	0.546	N	0.798	0.398	None	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	0	2.67E-05	0
I/T	rs373690962	-2.826	0.546	N	0.798	0.398	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
I/T	rs373690962	-2.826	0.546	N	0.798	0.398	None	gnomAD-4.0.0	4.96079E-06	None	None	None	None	N	None	0	0	None	0	4.46249E-05	None	0	0	5.08718E-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
I/A	0.7237	likely_pathogenic	0.7016	pathogenic	-2.638	Highly Destabilizing	0.397	N	0.712	prob.delet.	None	None	None	None	N
I/C	0.9439	likely_pathogenic	0.9461	pathogenic	-1.722	Destabilizing	0.992	D	0.758	deleterious	None	None	None	None	N
I/D	0.9937	likely_pathogenic	0.9937	pathogenic	-3.247	Highly Destabilizing	0.972	D	0.851	deleterious	None	None	None	None	N
I/E	0.9643	likely_pathogenic	0.9641	pathogenic	-3.032	Highly Destabilizing	0.919	D	0.839	deleterious	None	None	None	None	N
I/F	0.5465	ambiguous	0.5523	ambiguous	-1.695	Destabilizing	0.737	D	0.752	deleterious	None	None	None	None	N
I/G	0.975	likely_pathogenic	0.9734	pathogenic	-3.152	Highly Destabilizing	0.919	D	0.816	deleterious	None	None	None	None	N
I/H	0.9709	likely_pathogenic	0.9695	pathogenic	-2.61	Highly Destabilizing	0.992	D	0.809	deleterious	None	None	None	None	N
I/K	0.9298	likely_pathogenic	0.9203	pathogenic	-2.185	Highly Destabilizing	0.895	D	0.83	deleterious	N	0.503312831	None	None	N
I/L	0.2694	likely_benign	0.2507	benign	-1.144	Destabilizing	0.002	N	0.239	neutral	N	0.492204638	None	None	N
I/M	0.2233	likely_benign	0.2157	benign	-0.879	Destabilizing	0.808	D	0.755	deleterious	N	0.479332773	None	None	N
I/N	0.9509	likely_pathogenic	0.9502	pathogenic	-2.508	Highly Destabilizing	0.972	D	0.829	deleterious	None	None	None	None	N
I/P	0.9889	likely_pathogenic	0.9891	pathogenic	-1.626	Destabilizing	0.972	D	0.839	deleterious	None	None	None	None	N
I/Q	0.9379	likely_pathogenic	0.933	pathogenic	-2.42	Highly Destabilizing	0.972	D	0.806	deleterious	None	None	None	None	N
I/R	0.8957	likely_pathogenic	0.8828	pathogenic	-1.802	Destabilizing	0.895	D	0.833	deleterious	N	0.486133629	None	None	N
I/S	0.888	likely_pathogenic	0.8803	pathogenic	-3.108	Highly Destabilizing	0.919	D	0.751	deleterious	None	None	None	None	N
I/T	0.4988	ambiguous	0.4784	ambiguous	-2.759	Highly Destabilizing	0.546	D	0.798	deleterious	N	0.502045384	None	None	N
I/V	0.0708	likely_benign	0.0694	benign	-1.626	Destabilizing	0.007	N	0.18	neutral	N	0.426462436	None	None	N
I/W	0.976	likely_pathogenic	0.9757	pathogenic	-2.139	Highly Destabilizing	0.992	D	0.796	deleterious	None	None	None	None	N
I/Y	0.933	likely_pathogenic	0.9404	pathogenic	-1.838	Destabilizing	0.919	D	0.801	deleterious	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.