TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27957	84094;84095;84096	chr2:178562263;178562262;178562261	chr2:179426990;179426989;179426988
N2AB	26316	79171;79172;79173	chr2:178562263;178562262;178562261	chr2:179426990;179426989;179426988
N2A	25389	76390;76391;76392	chr2:178562263;178562262;178562261	chr2:179426990;179426989;179426988
N2B	18892	56899;56900;56901	chr2:178562263;178562262;178562261	chr2:179426990;179426989;179426988
Novex-1	19017	57274;57275;57276	chr2:178562263;178562262;178562261	chr2:179426990;179426989;179426988
Novex-2	19084	57475;57476;57477	chr2:178562263;178562262;178562261	chr2:179426990;179426989;179426988
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Fn3-91
• Domain position: 95
• Structural Position: 131
• Q(SASA): 0.5423
• 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/K	rs148067743	-0.366	None	N	0.081	0.112	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
R/K	rs148067743	-0.366	None	N	0.081	0.112	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
R/K	rs148067743	-0.366	None	N	0.081	0.112	None	gnomAD-4.0.0	1.85949E-06	None	None	None	None	N	None	1.33294E-05	0	None	0	0	None	0	0	1.69547E-06	0	0
R/M	None	None	0.57	N	0.369	0.127	0.210429274316	gnomAD-4.0.0	6.84421E-07	None	None	None	None	N	None	0	0	None	0	0	None	1.87554E-05	0	0	0	0
R/T	rs148067743	-0.326	0.058	N	0.383	0.082	0.185906805712	gnomAD-2.1.1	1.45153E-04	None	None	None	None	N	None	0	8.71536E-04	None	0	0	None	0	None	0	4.45E-05	1.66279E-04
R/T	rs148067743	-0.326	0.058	N	0.383	0.082	0.185906805712	gnomAD-3.1.2	1.51183E-04	None	None	None	None	N	None	4.83E-05	9.17071E-04	0	0	0	None	0	0	2.94E-05	0	2.39234E-03
R/T	rs148067743	-0.326	0.058	N	0.383	0.082	0.185906805712	1000 genomes	3.99361E-04	None	None	None	None	N	None	0	0	None	None	0	2E-03	None	None	None	0	None
R/T	rs148067743	-0.326	0.058	N	0.383	0.082	0.185906805712	gnomAD-4.0.0	6.07436E-05	None	None	None	None	N	None	5.33177E-05	9.50444E-04	None	0	0	None	0	0	2.45844E-05	0	1.28078E-04

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	0.456	ambiguous	0.5109	ambiguous	-0.564	Destabilizing	0.016	N	0.373	neutral	None	None	None	None	N
R/C	0.2929	likely_benign	0.3142	benign	-0.544	Destabilizing	0.869	D	0.394	neutral	None	None	None	None	N
R/D	0.8225	likely_pathogenic	0.851	pathogenic	0.068	Stabilizing	0.075	N	0.389	neutral	None	None	None	None	N
R/E	0.4342	ambiguous	0.4722	ambiguous	0.172	Stabilizing	0.016	N	0.267	neutral	None	None	None	None	N
R/F	0.7381	likely_pathogenic	0.7781	pathogenic	-0.568	Destabilizing	0.637	D	0.448	neutral	None	None	None	None	N
R/G	0.3256	likely_benign	0.3916	ambiguous	-0.835	Destabilizing	0.058	N	0.421	neutral	N	0.489321836	None	None	N
R/H	0.1582	likely_benign	0.1618	benign	-1.232	Destabilizing	0.366	N	0.273	neutral	None	None	None	None	N
R/I	0.4345	ambiguous	0.4828	ambiguous	0.145	Stabilizing	0.366	N	0.49	neutral	None	None	None	None	N
R/K	0.0682	likely_benign	0.0658	benign	-0.515	Destabilizing	None	N	0.081	neutral	N	0.348732371	None	None	N
R/L	0.3821	ambiguous	0.4345	ambiguous	0.145	Stabilizing	0.075	N	0.421	neutral	None	None	None	None	N
R/M	0.3343	likely_benign	0.3871	ambiguous	-0.207	Destabilizing	0.57	D	0.369	neutral	N	0.490015269	None	None	N
R/N	0.6294	likely_pathogenic	0.6668	pathogenic	-0.075	Destabilizing	0.075	N	0.259	neutral	None	None	None	None	N
R/P	0.9403	likely_pathogenic	0.9575	pathogenic	-0.07	Destabilizing	0.141	N	0.454	neutral	None	None	None	None	N
R/Q	0.1207	likely_benign	0.1235	benign	-0.236	Destabilizing	0.039	N	0.293	neutral	None	None	None	None	N
R/S	0.5228	ambiguous	0.5809	pathogenic	-0.755	Destabilizing	0.012	N	0.366	neutral	N	0.511523905	None	None	N
R/T	0.2681	likely_benign	0.3081	benign	-0.48	Destabilizing	0.058	N	0.383	neutral	N	0.488455044	None	None	N
R/V	0.4522	ambiguous	0.4811	ambiguous	-0.07	Destabilizing	0.075	N	0.467	neutral	None	None	None	None	N
R/W	0.331	likely_benign	0.4034	ambiguous	-0.349	Destabilizing	0.833	D	0.453	neutral	N	0.48429675	None	None	N
R/Y	0.6015	likely_pathogenic	0.6382	pathogenic	-0.013	Destabilizing	0.637	D	0.522	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.