TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9751	29476;29477;29478	chr2:178706623;178706622;178706621	chr2:179571350;179571349;179571348
N2AB	9434	28525;28526;28527	chr2:178706623;178706622;178706621	chr2:179571350;179571349;179571348
N2A	8507	25744;25745;25746	chr2:178706623;178706622;178706621	chr2:179571350;179571349;179571348
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: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-83
• Domain position: 54
• Structural Position: 131
• Q(SASA): 0.427
• 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
G/V	rs779884658	-0.149	0.994	None	0.796	0.339	0.386395597597	gnomAD-2.1.1	1.2E-05	None	None	None	None	I	None	0	0	None	0	0	None	9.8E-05	None	0	0	0
G/V	rs779884658	-0.149	0.994	None	0.796	0.339	0.386395597597	gnomAD-4.0.0	8.89413E-06	None	None	None	None	I	None	0	2.23604E-05	None	0	0	None	0	0	2.69828E-06	1.04343E-04	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
G/A	0.4889	ambiguous	0.3129	benign	-0.324	Destabilizing	0.961	D	0.521	neutral	None	None	None	None	I
G/C	0.8248	likely_pathogenic	0.6377	pathogenic	-0.748	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
G/D	0.4058	ambiguous	0.2772	benign	-1.001	Destabilizing	0.153	N	0.528	neutral	None	None	None	None	I
G/E	0.549	ambiguous	0.3613	ambiguous	-1.174	Destabilizing	0.983	D	0.721	prob.delet.	None	None	None	None	I
G/F	0.9549	likely_pathogenic	0.8786	pathogenic	-1.101	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
G/H	0.8817	likely_pathogenic	0.7503	pathogenic	-0.654	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	I
G/I	0.9188	likely_pathogenic	0.7541	pathogenic	-0.47	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	I
G/K	0.8244	likely_pathogenic	0.6806	pathogenic	-0.987	Destabilizing	0.991	D	0.733	prob.delet.	None	None	None	None	I
G/L	0.9123	likely_pathogenic	0.7941	pathogenic	-0.47	Destabilizing	0.996	D	0.791	deleterious	None	None	None	None	I
G/M	0.9182	likely_pathogenic	0.8035	pathogenic	-0.405	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
G/N	0.5708	likely_pathogenic	0.4098	ambiguous	-0.519	Destabilizing	0.983	D	0.677	prob.neutral	None	None	None	None	I
G/P	0.9856	likely_pathogenic	0.9497	pathogenic	-0.388	Destabilizing	0.996	D	0.764	deleterious	None	None	None	None	I
G/Q	0.7925	likely_pathogenic	0.6107	pathogenic	-0.861	Destabilizing	0.991	D	0.775	deleterious	None	None	None	None	I
G/R	0.786	likely_pathogenic	0.574	pathogenic	-0.46	Destabilizing	0.989	D	0.775	deleterious	None	None	None	None	I
G/S	0.3769	ambiguous	0.2249	benign	-0.579	Destabilizing	0.978	D	0.629	neutral	None	None	None	None	I
G/T	0.7555	likely_pathogenic	0.5202	ambiguous	-0.7	Destabilizing	0.991	D	0.728	prob.delet.	None	None	None	None	I
G/V	0.8311	likely_pathogenic	0.5843	pathogenic	-0.388	Destabilizing	0.994	D	0.796	deleterious	None	None	None	None	I
G/W	0.882	likely_pathogenic	0.7023	pathogenic	-1.264	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
G/Y	0.8896	likely_pathogenic	0.7407	pathogenic	-0.93	Destabilizing	1.0	D	0.777	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.