TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8126	24601;24602;24603	chr2:178718824;178718823;178718822	chr2:179583551;179583550;179583549
N2AB	7809	23650;23651;23652	chr2:178718824;178718823;178718822	chr2:179583551;179583550;179583549
N2A	6882	20869;20870;20871	chr2:178718824;178718823;178718822	chr2:179583551;179583550;179583549
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-66
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.2638
• 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
I/V	rs764456853	-1.049	0.899	N	0.293	0.183	0.486993258117	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	1.65782E-04
I/V	rs764456853	-1.049	0.899	N	0.293	0.183	0.486993258117	gnomAD-4.0.0	1.16315E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.43916E-05	1.15934E-05	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	0.5537	ambiguous	0.5739	pathogenic	-2.119	Highly Destabilizing	0.993	D	0.537	neutral	None	None	None	None	I
I/C	0.7764	likely_pathogenic	0.8033	pathogenic	-1.319	Destabilizing	1.0	D	0.604	neutral	None	None	None	None	I
I/D	0.8503	likely_pathogenic	0.8692	pathogenic	-1.759	Destabilizing	0.999	D	0.694	prob.neutral	None	None	None	None	I
I/E	0.7564	likely_pathogenic	0.7802	pathogenic	-1.683	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	I
I/F	0.1404	likely_benign	0.1886	benign	-1.448	Destabilizing	0.135	N	0.201	neutral	N	0.488672205	None	None	I
I/G	0.8173	likely_pathogenic	0.8367	pathogenic	-2.537	Highly Destabilizing	0.999	D	0.665	neutral	None	None	None	None	I
I/H	0.6103	likely_pathogenic	0.6627	pathogenic	-1.857	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
I/K	0.5659	likely_pathogenic	0.6084	pathogenic	-1.383	Destabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	I
I/L	0.1392	likely_benign	0.1522	benign	-0.989	Destabilizing	0.817	D	0.267	neutral	N	0.488530393	None	None	I
I/M	0.1294	likely_benign	0.1462	benign	-0.779	Destabilizing	0.999	D	0.521	neutral	N	0.498027048	None	None	I
I/N	0.4814	ambiguous	0.5094	ambiguous	-1.287	Destabilizing	0.999	D	0.717	prob.delet.	D	0.529453072	None	None	I
I/P	0.8965	likely_pathogenic	0.9184	pathogenic	-1.339	Destabilizing	0.999	D	0.72	prob.delet.	None	None	None	None	I
I/Q	0.6053	likely_pathogenic	0.6449	pathogenic	-1.386	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	I
I/R	0.4347	ambiguous	0.488	ambiguous	-0.909	Destabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	I
I/S	0.4791	ambiguous	0.4996	ambiguous	-1.98	Destabilizing	0.999	D	0.63	neutral	N	0.512398774	None	None	I
I/T	0.4157	ambiguous	0.4149	ambiguous	-1.777	Destabilizing	0.997	D	0.568	neutral	N	0.493952124	None	None	I
I/V	0.0923	likely_benign	0.0943	benign	-1.339	Destabilizing	0.899	D	0.293	neutral	N	0.493055574	None	None	I
I/W	0.7602	likely_pathogenic	0.8193	pathogenic	-1.627	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
I/Y	0.4715	ambiguous	0.5343	ambiguous	-1.382	Destabilizing	0.971	D	0.573	neutral	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.