TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31061	93406;93407;93408	chr2:178548445;178548444;178548443	chr2:179413172;179413171;179413170
N2AB	29420	88483;88484;88485	chr2:178548445;178548444;178548443	chr2:179413172;179413171;179413170
N2A	28493	85702;85703;85704	chr2:178548445;178548444;178548443	chr2:179413172;179413171;179413170
N2B	21996	66211;66212;66213	chr2:178548445;178548444;178548443	chr2:179413172;179413171;179413170
Novex-1	22121	66586;66587;66588	chr2:178548445;178548444;178548443	chr2:179413172;179413171;179413170
Novex-2	22188	66787;66788;66789	chr2:178548445;178548444;178548443	chr2:179413172;179413171;179413170
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Fn3-114
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.871
• 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
R/C	rs768270597	-0.219	1.0	N	0.479	0.317	0.659234351692	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	8.92E-06	0
R/C	rs768270597	-0.219	1.0	N	0.479	0.317	0.659234351692	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
R/C	rs768270597	-0.219	1.0	N	0.479	0.317	0.659234351692	gnomAD-4.0.0	3.71818E-06	None	None	None	None	N	None	2.67065E-05	0	None	0	2.22826E-05	None	0	0	2.54279E-06	0	0
R/H	rs727504923	-0.532	0.999	N	0.506	0.284	None	gnomAD-2.1.1	3.58E-05	None	None	None	None	N	None	2.06714E-04	0	None	0	0	None	0	None	0	3.92E-05	0
R/H	rs727504923	-0.532	0.999	N	0.506	0.284	None	gnomAD-3.1.2	7.89E-05	None	None	None	None	N	None	2.41359E-04	6.55E-05	0	0	0	None	0	0	1.47E-05	0	0
R/H	rs727504923	-0.532	0.999	N	0.506	0.284	None	gnomAD-4.0.0	2.66461E-05	None	None	None	None	N	None	2.26957E-04	3.33356E-05	None	0	0	None	0	0	1.8647E-05	1.09786E-05	1.60102E-05
R/P	rs727504923	None	0.998	N	0.493	0.282	0.408172294925	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/P	rs727504923	None	0.998	N	0.493	0.282	0.408172294925	gnomAD-4.0.0	6.57246E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47011E-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
R/A	0.842	likely_pathogenic	0.7411	pathogenic	-0.071	Destabilizing	0.927	D	0.449	neutral	None	None	None	None	N
R/C	0.4446	ambiguous	0.4001	ambiguous	-0.386	Destabilizing	1.0	D	0.479	neutral	N	0.497284173	None	None	N
R/D	0.9627	likely_pathogenic	0.933	pathogenic	-0.373	Destabilizing	0.997	D	0.489	neutral	None	None	None	None	N
R/E	0.8678	likely_pathogenic	0.7871	pathogenic	-0.347	Destabilizing	0.99	D	0.498	neutral	None	None	None	None	N
R/F	0.8576	likely_pathogenic	0.793	pathogenic	-0.424	Destabilizing	0.982	D	0.483	neutral	None	None	None	None	N
R/G	0.706	likely_pathogenic	0.5914	pathogenic	-0.182	Destabilizing	0.994	D	0.474	neutral	N	0.448634714	None	None	N
R/H	0.2893	likely_benign	0.2501	benign	-0.608	Destabilizing	0.999	D	0.506	neutral	N	0.474153488	None	None	N
R/I	0.6611	likely_pathogenic	0.5614	ambiguous	0.175	Stabilizing	0.884	D	0.457	neutral	None	None	None	None	N
R/K	0.224	likely_benign	0.1797	benign	-0.318	Destabilizing	0.975	D	0.471	neutral	None	None	None	None	N
R/L	0.4793	ambiguous	0.3911	ambiguous	0.175	Stabilizing	0.037	N	0.294	neutral	N	0.472765155	None	None	N
R/M	0.6753	likely_pathogenic	0.5587	ambiguous	-0.187	Destabilizing	0.982	D	0.478	neutral	None	None	None	None	N
R/N	0.914	likely_pathogenic	0.852	pathogenic	-0.246	Destabilizing	0.997	D	0.476	neutral	None	None	None	None	N
R/P	0.8489	likely_pathogenic	0.7594	pathogenic	0.109	Stabilizing	0.998	D	0.493	neutral	N	0.494775223	None	None	N
R/Q	0.2768	likely_benign	0.2212	benign	-0.281	Destabilizing	0.997	D	0.471	neutral	None	None	None	None	N
R/S	0.9107	likely_pathogenic	0.8508	pathogenic	-0.414	Destabilizing	0.994	D	0.503	neutral	N	0.469647492	None	None	N
R/T	0.7982	likely_pathogenic	0.6767	pathogenic	-0.295	Destabilizing	0.969	D	0.473	neutral	None	None	None	None	N
R/V	0.7418	likely_pathogenic	0.6483	pathogenic	0.109	Stabilizing	0.884	D	0.431	neutral	None	None	None	None	N
R/W	0.469	ambiguous	0.4093	ambiguous	-0.619	Destabilizing	0.999	D	0.489	neutral	None	None	None	None	N
R/Y	0.7025	likely_pathogenic	0.6202	pathogenic	-0.233	Destabilizing	0.997	D	0.487	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.