TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14666	44221;44222;44223	chr2:178631052;178631051;178631050	chr2:179495779;179495778;179495777
N2AB	13025	39298;39299;39300	chr2:178631052;178631051;178631050	chr2:179495779;179495778;179495777
N2A	12098	36517;36518;36519	chr2:178631052;178631051;178631050	chr2:179495779;179495778;179495777
N2B	5601	17026;17027;17028	chr2:178631052;178631051;178631050	chr2:179495779;179495778;179495777
Novex-1	5726	17401;17402;17403	chr2:178631052;178631051;178631050	chr2:179495779;179495778;179495777
Novex-2	5793	17602;17603;17604	chr2:178631052;178631051;178631050	chr2:179495779;179495778;179495777
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-97
• Domain position: 81
• Structural Position: 172
• Q(SASA): 0.2481
• 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	rs756959571	-0.223	0.627	N	0.671	0.235	0.358134431457	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
G/R	rs756959571	-0.223	0.627	N	0.671	0.235	0.358134431457	gnomAD-4.0.0	4.77867E-06	None	None	None	None	N	None	0	4.57854E-05	None	0	0	None	0	0	2.85992E-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
G/A	0.0814	likely_benign	0.1	benign	-0.804	Destabilizing	None	N	0.247	neutral	N	0.273979074	None	None	N
G/C	0.3444	ambiguous	0.4241	ambiguous	-1.382	Destabilizing	0.005	N	0.531	neutral	None	None	None	None	N
G/D	0.9112	likely_pathogenic	0.9479	pathogenic	-1.53	Destabilizing	0.388	N	0.637	neutral	None	None	None	None	N
G/E	0.8745	likely_pathogenic	0.9327	pathogenic	-1.548	Destabilizing	0.324	N	0.643	neutral	N	0.44954129	None	None	N
G/F	0.937	likely_pathogenic	0.9574	pathogenic	-1.17	Destabilizing	0.818	D	0.71	prob.delet.	None	None	None	None	N
G/H	0.9415	likely_pathogenic	0.9682	pathogenic	-1.379	Destabilizing	0.981	D	0.662	neutral	None	None	None	None	N
G/I	0.7177	likely_pathogenic	0.8183	pathogenic	-0.325	Destabilizing	0.69	D	0.7	prob.neutral	None	None	None	None	N
G/K	0.9443	likely_pathogenic	0.9719	pathogenic	-1.174	Destabilizing	0.388	N	0.643	neutral	None	None	None	None	N
G/L	0.7785	likely_pathogenic	0.8493	pathogenic	-0.325	Destabilizing	0.241	N	0.635	neutral	None	None	None	None	N
G/M	0.8537	likely_pathogenic	0.9026	pathogenic	-0.436	Destabilizing	0.944	D	0.681	prob.neutral	None	None	None	None	N
G/N	0.8905	likely_pathogenic	0.9367	pathogenic	-1.049	Destabilizing	0.388	N	0.647	neutral	None	None	None	None	N
G/P	0.9936	likely_pathogenic	0.9959	pathogenic	-0.444	Destabilizing	0.818	D	0.68	prob.neutral	None	None	None	None	N
G/Q	0.8761	likely_pathogenic	0.9291	pathogenic	-1.21	Destabilizing	0.818	D	0.693	prob.neutral	None	None	None	None	N
G/R	0.813	likely_pathogenic	0.8981	pathogenic	-0.942	Destabilizing	0.627	D	0.671	neutral	N	0.448765882	None	None	N
G/S	0.1606	likely_benign	0.2051	benign	-1.369	Destabilizing	0.024	N	0.289	neutral	None	None	None	None	N
G/T	0.4461	ambiguous	0.5763	pathogenic	-1.297	Destabilizing	0.241	N	0.617	neutral	None	None	None	None	N
G/V	0.4726	ambiguous	0.6004	pathogenic	-0.444	Destabilizing	0.193	N	0.643	neutral	N	0.440960954	None	None	N
G/W	0.9222	likely_pathogenic	0.95	pathogenic	-1.538	Destabilizing	0.981	D	0.684	prob.neutral	None	None	None	None	N
G/Y	0.9179	likely_pathogenic	0.9509	pathogenic	-1.088	Destabilizing	0.932	D	0.694	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.