TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27563	82912;82913;82914	chr2:178563445;178563444;178563443	chr2:179428172;179428171;179428170
N2AB	25922	77989;77990;77991	chr2:178563445;178563444;178563443	chr2:179428172;179428171;179428170
N2A	24995	75208;75209;75210	chr2:178563445;178563444;178563443	chr2:179428172;179428171;179428170
N2B	18498	55717;55718;55719	chr2:178563445;178563444;178563443	chr2:179428172;179428171;179428170
Novex-1	18623	56092;56093;56094	chr2:178563445;178563444;178563443	chr2:179428172;179428171;179428170
Novex-2	18690	56293;56294;56295	chr2:178563445;178563444;178563443	chr2:179428172;179428171;179428170
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: Fn3-88
• Domain position: 95
• Structural Position: 129
• Q(SASA): 0.4891
• 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	rs72648214	-0.406	0.991	N	0.39	0.371	0.534239989213	gnomAD-2.1.1	3.22E-05	None	None	None	None	N	None	0	0	None	0	1.11995E-04	None	0	None	0	5.34E-05	0
R/C	rs72648214	-0.406	0.991	N	0.39	0.371	0.534239989213	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
R/C	rs72648214	-0.406	0.991	N	0.39	0.371	0.534239989213	gnomAD-4.0.0	1.23962E-05	None	None	None	None	N	None	1.33622E-05	0	None	0	8.93256E-05	None	0	1.64474E-04	1.10195E-05	1.09791E-05	0
R/H	rs118079537	-1.001	0.01	N	0.234	0.1	None	gnomAD-2.1.1	2.50275E-04	None	None	None	None	N	None	0	1.13231E-04	None	0	3.14077E-03	None	6.54E-05	None	0	2.35E-05	0
R/H	rs118079537	-1.001	0.01	N	0.234	0.1	None	gnomAD-3.1.2	1.31574E-04	None	None	None	None	N	None	0	0	0	0	3.48702E-03	None	0	0	2.94E-05	0	0
R/H	rs118079537	-1.001	0.01	N	0.234	0.1	None	1000 genomes	5.99042E-04	None	None	None	None	N	None	0	0	None	None	3E-03	0	None	None	None	0	None
R/H	rs118079537	-1.001	0.01	N	0.234	0.1	None	gnomAD-4.0.0	6.75517E-05	None	None	None	None	N	None	0	5.00367E-05	None	0	1.69726E-03	None	0	0	2.2039E-05	2.19587E-05	3.20123E-05
R/S	rs72648214	None	0.208	N	0.406	0.241	0.253205268125	gnomAD-4.0.0	6.84261E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99489E-07	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	0.3029	likely_benign	0.3639	ambiguous	-0.312	Destabilizing	0.064	N	0.419	neutral	None	None	None	None	N
R/C	0.1473	likely_benign	0.1624	benign	-0.331	Destabilizing	0.991	D	0.39	neutral	N	0.518092013	None	None	N
R/D	0.6131	likely_pathogenic	0.6788	pathogenic	-0.169	Destabilizing	0.25	N	0.424	neutral	None	None	None	None	N
R/E	0.302	likely_benign	0.3615	ambiguous	-0.123	Destabilizing	0.121	N	0.367	neutral	None	None	None	None	N
R/F	0.4456	ambiguous	0.4995	ambiguous	-0.591	Destabilizing	0.703	D	0.429	neutral	None	None	None	None	N
R/G	0.2555	likely_benign	0.299	benign	-0.493	Destabilizing	0.001	N	0.305	neutral	N	0.473451791	None	None	N
R/H	0.0897	likely_benign	0.0969	benign	-0.873	Destabilizing	0.01	N	0.234	neutral	N	0.508760454	None	None	N
R/I	0.2009	likely_benign	0.2237	benign	0.128	Stabilizing	0.703	D	0.447	neutral	None	None	None	None	N
R/K	0.0841	likely_benign	0.0993	benign	-0.315	Destabilizing	0.001	N	0.123	neutral	None	None	None	None	N
R/L	0.1678	likely_benign	0.1964	benign	0.128	Stabilizing	0.389	N	0.442	neutral	N	0.423872343	None	None	N
R/M	0.2095	likely_benign	0.2426	benign	-0.068	Destabilizing	0.878	D	0.456	neutral	None	None	None	None	N
R/N	0.4963	ambiguous	0.5704	pathogenic	0.055	Stabilizing	0.143	N	0.387	neutral	None	None	None	None	N
R/P	0.459	ambiguous	0.5148	ambiguous	0.001	Stabilizing	0.932	D	0.478	neutral	N	0.461677412	None	None	N
R/Q	0.0927	likely_benign	0.1002	benign	-0.166	Destabilizing	0.25	N	0.463	neutral	None	None	None	None	N
R/S	0.3759	ambiguous	0.4484	ambiguous	-0.428	Destabilizing	0.208	N	0.406	neutral	N	0.48174721	None	None	N
R/T	0.1508	likely_benign	0.1891	benign	-0.257	Destabilizing	0.403	N	0.42	neutral	None	None	None	None	N
R/V	0.2346	likely_benign	0.2774	benign	0.001	Stabilizing	0.403	N	0.491	neutral	None	None	None	None	N
R/W	0.1528	likely_benign	0.1656	benign	-0.552	Destabilizing	0.964	D	0.413	neutral	None	None	None	None	N
R/Y	0.3099	likely_benign	0.3441	ambiguous	-0.166	Destabilizing	0.369	N	0.461	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.