TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7180	21763;21764;21765	chr2:178723562;178723561;178723560	chr2:179588289;179588288;179588287
N2AB	6863	20812;20813;20814	chr2:178723562;178723561;178723560	chr2:179588289;179588288;179588287
N2A	5936	18031;18032;18033	chr2:178723562;178723561;178723560	chr2:179588289;179588288;179588287
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: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-56
• Domain position: 44
• Structural Position: 73
• Q(SASA): 0.3183
• 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
G/R	rs760549917	-0.33	0.595	N	0.413	0.34	0.395289904662	gnomAD-2.1.1	3.62E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8E-05	0
G/R	rs760549917	-0.33	0.595	N	0.413	0.34	0.395289904662	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
G/R	rs760549917	-0.33	0.595	N	0.413	0.34	0.395289904662	gnomAD-4.0.0	1.85951E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.56299E-05	0	2.45845E-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
G/A	0.1998	likely_benign	0.2196	benign	-0.235	Destabilizing	0.978	D	0.415	neutral	N	0.484889639	None	None	N
G/C	0.4488	ambiguous	0.4918	ambiguous	-0.773	Destabilizing	1.0	D	0.63	neutral	None	None	None	None	N
G/D	0.152	likely_benign	0.1592	benign	-0.676	Destabilizing	0.998	D	0.455	neutral	None	None	None	None	N
G/E	0.2349	likely_benign	0.2659	benign	-0.846	Destabilizing	0.997	D	0.48	neutral	N	0.464049906	None	None	N
G/F	0.7781	likely_pathogenic	0.7983	pathogenic	-1.026	Destabilizing	1.0	D	0.619	neutral	None	None	None	None	N
G/H	0.5493	ambiguous	0.581	pathogenic	-0.515	Destabilizing	1.0	D	0.528	neutral	None	None	None	None	N
G/I	0.5928	likely_pathogenic	0.6388	pathogenic	-0.415	Destabilizing	0.998	D	0.629	neutral	None	None	None	None	N
G/K	0.5532	ambiguous	0.5994	pathogenic	-0.821	Destabilizing	0.995	D	0.483	neutral	None	None	None	None	N
G/L	0.621	likely_pathogenic	0.6566	pathogenic	-0.415	Destabilizing	0.998	D	0.601	neutral	None	None	None	None	N
G/M	0.6367	likely_pathogenic	0.6745	pathogenic	-0.456	Destabilizing	1.0	D	0.616	neutral	None	None	None	None	N
G/N	0.2782	likely_benign	0.2779	benign	-0.389	Destabilizing	0.998	D	0.477	neutral	None	None	None	None	N
G/P	0.913	likely_pathogenic	0.9249	pathogenic	-0.324	Destabilizing	0.999	D	0.519	neutral	None	None	None	None	N
G/Q	0.4737	ambiguous	0.5152	ambiguous	-0.692	Destabilizing	0.998	D	0.519	neutral	None	None	None	None	N
G/R	0.4509	ambiguous	0.4954	ambiguous	-0.36	Destabilizing	0.595	D	0.413	neutral	N	0.483750777	None	None	N
G/S	0.1136	likely_benign	0.1191	benign	-0.493	Destabilizing	0.914	D	0.261	neutral	None	None	None	None	N
G/T	0.2031	likely_benign	0.2191	benign	-0.602	Destabilizing	0.784	D	0.401	neutral	None	None	None	None	N
G/V	0.3808	ambiguous	0.4256	ambiguous	-0.324	Destabilizing	0.997	D	0.613	neutral	N	0.486157087	None	None	N
G/W	0.5458	ambiguous	0.5754	pathogenic	-1.184	Destabilizing	1.0	D	0.572	neutral	None	None	None	None	N
G/Y	0.6016	likely_pathogenic	0.6292	pathogenic	-0.838	Destabilizing	1.0	D	0.615	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.