TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26361	79306;79307;79308	chr2:178567051;178567050;178567049	chr2:179431778;179431777;179431776
N2AB	24720	74383;74384;74385	chr2:178567051;178567050;178567049	chr2:179431778;179431777;179431776
N2A	23793	71602;71603;71604	chr2:178567051;178567050;178567049	chr2:179431778;179431777;179431776
N2B	17296	52111;52112;52113	chr2:178567051;178567050;178567049	chr2:179431778;179431777;179431776
Novex-1	17421	52486;52487;52488	chr2:178567051;178567050;178567049	chr2:179431778;179431777;179431776
Novex-2	17488	52687;52688;52689	chr2:178567051;178567050;178567049	chr2:179431778;179431777;179431776
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: Fn3-79
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0517
• 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/M	rs776297490	-2.316	0.782	N	0.603	0.362	0.53832913131	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
I/M	rs776297490	-2.316	0.782	N	0.603	0.362	0.53832913131	gnomAD-4.0.0	1.16326E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.52925E-05	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	0.9553	likely_pathogenic	0.9565	pathogenic	-3.172	Highly Destabilizing	0.218	N	0.592	neutral	None	None	None	None	N
I/C	0.9412	likely_pathogenic	0.942	pathogenic	-2.371	Highly Destabilizing	0.973	D	0.733	prob.delet.	None	None	None	None	N
I/D	0.9994	likely_pathogenic	0.9995	pathogenic	-3.925	Highly Destabilizing	0.906	D	0.837	deleterious	None	None	None	None	N
I/E	0.9982	likely_pathogenic	0.9983	pathogenic	-3.627	Highly Destabilizing	0.906	D	0.821	deleterious	None	None	None	None	N
I/F	0.7493	likely_pathogenic	0.759	pathogenic	-1.962	Destabilizing	0.826	D	0.606	neutral	None	None	None	None	N
I/G	0.9933	likely_pathogenic	0.9937	pathogenic	-3.718	Highly Destabilizing	0.906	D	0.802	deleterious	None	None	None	None	N
I/H	0.9979	likely_pathogenic	0.9979	pathogenic	-3.228	Highly Destabilizing	0.991	D	0.85	deleterious	None	None	None	None	N
I/K	0.9965	likely_pathogenic	0.9967	pathogenic	-2.674	Highly Destabilizing	0.879	D	0.823	deleterious	N	0.51105415	None	None	N
I/L	0.3253	likely_benign	0.3586	ambiguous	-1.504	Destabilizing	0.084	N	0.258	neutral	N	0.508400668	None	None	N
I/M	0.4257	ambiguous	0.4439	ambiguous	-1.629	Destabilizing	0.782	D	0.603	neutral	N	0.499190866	None	None	N
I/N	0.9918	likely_pathogenic	0.9922	pathogenic	-3.353	Highly Destabilizing	0.967	D	0.857	deleterious	None	None	None	None	N
I/P	0.9963	likely_pathogenic	0.9967	pathogenic	-2.056	Highly Destabilizing	0.967	D	0.843	deleterious	None	None	None	None	N
I/Q	0.9969	likely_pathogenic	0.997	pathogenic	-3.068	Highly Destabilizing	0.967	D	0.86	deleterious	None	None	None	None	N
I/R	0.9948	likely_pathogenic	0.9951	pathogenic	-2.517	Highly Destabilizing	0.879	D	0.859	deleterious	N	0.51105415	None	None	N
I/S	0.9851	likely_pathogenic	0.9851	pathogenic	-3.855	Highly Destabilizing	0.826	D	0.767	deleterious	None	None	None	None	N
I/T	0.9595	likely_pathogenic	0.9589	pathogenic	-3.418	Highly Destabilizing	0.505	D	0.535	neutral	N	0.499444355	None	None	N
I/V	0.085	likely_benign	0.0867	benign	-2.056	Highly Destabilizing	None	N	0.197	neutral	N	0.322232763	None	None	N
I/W	0.997	likely_pathogenic	0.9975	pathogenic	-2.332	Highly Destabilizing	0.991	D	0.825	deleterious	None	None	None	None	N
I/Y	0.9858	likely_pathogenic	0.9865	pathogenic	-2.212	Highly Destabilizing	0.906	D	0.692	prob.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.