TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14448	43567;43568;43569	chr2:178632664;178632663;178632662	chr2:179497391;179497390;179497389
N2AB	12807	38644;38645;38646	chr2:178632664;178632663;178632662	chr2:179497391;179497390;179497389
N2A	11880	35863;35864;35865	chr2:178632664;178632663;178632662	chr2:179497391;179497390;179497389
N2B	5383	16372;16373;16374	chr2:178632664;178632663;178632662	chr2:179497391;179497390;179497389
Novex-1	5508	16747;16748;16749	chr2:178632664;178632663;178632662	chr2:179497391;179497390;179497389
Novex-2	5575	16948;16949;16950	chr2:178632664;178632663;178632662	chr2:179497391;179497390;179497389
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-95
• Domain position: 41
• Structural Position: 59
• Q(SASA): 0.6059
• 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
T/A	rs773346487	-0.075	None	N	0.096	0.115	0.0551355673512	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.95E-06	0
T/A	rs773346487	-0.075	None	N	0.096	0.115	0.0551355673512	gnomAD-4.0.0	1.59188E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85971E-06	0	0
T/I	rs545318911	0.123	None	N	0.206	0.159	0.231873229951	gnomAD-2.1.1	2.02E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	4.48E-05	0
T/I	rs545318911	0.123	None	N	0.206	0.159	0.231873229951	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07383E-04	0
T/I	rs545318911	0.123	None	N	0.206	0.159	0.231873229951	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
T/I	rs545318911	0.123	None	N	0.206	0.159	0.231873229951	gnomAD-4.0.0	6.40782E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.18312E-06	2.68068E-05	0
T/R	rs545318911	0.247	0.017	N	0.383	0.109	0.333906830038	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
T/R	rs545318911	0.247	0.017	N	0.383	0.109	0.333906830038	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/R	rs545318911	0.247	0.017	N	0.383	0.109	0.333906830038	gnomAD-4.0.0	6.57869E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47102E-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
T/A	0.0698	likely_benign	0.0737	benign	-0.258	Destabilizing	None	N	0.096	neutral	N	0.488444825	None	None	N
T/C	0.3959	ambiguous	0.3886	ambiguous	-0.411	Destabilizing	0.245	N	0.316	neutral	None	None	None	None	N
T/D	0.267	likely_benign	0.2818	benign	0.305	Stabilizing	0.018	N	0.381	neutral	None	None	None	None	N
T/E	0.1849	likely_benign	0.186	benign	0.248	Stabilizing	0.009	N	0.313	neutral	None	None	None	None	N
T/F	0.1928	likely_benign	0.1845	benign	-0.834	Destabilizing	0.044	N	0.463	neutral	None	None	None	None	N
T/G	0.2101	likely_benign	0.208	benign	-0.373	Destabilizing	0.009	N	0.299	neutral	None	None	None	None	N
T/H	0.1875	likely_benign	0.1857	benign	-0.515	Destabilizing	0.245	N	0.399	neutral	None	None	None	None	N
T/I	0.102	likely_benign	0.107	benign	-0.077	Destabilizing	None	N	0.206	neutral	N	0.487725552	None	None	N
T/K	0.1193	likely_benign	0.1141	benign	-0.219	Destabilizing	None	N	0.181	neutral	N	0.412426662	None	None	N
T/L	0.0848	likely_benign	0.082	benign	-0.077	Destabilizing	None	N	0.162	neutral	None	None	None	None	N
T/M	0.0884	likely_benign	0.0788	benign	-0.211	Destabilizing	0.138	N	0.345	neutral	None	None	None	None	N
T/N	0.1105	likely_benign	0.1165	benign	-0.16	Destabilizing	0.044	N	0.207	neutral	None	None	None	None	N
T/P	0.0905	likely_benign	0.0979	benign	-0.109	Destabilizing	0.033	N	0.411	neutral	N	0.469674404	None	None	N
T/Q	0.1719	likely_benign	0.1604	benign	-0.283	Destabilizing	0.001	N	0.22	neutral	None	None	None	None	N
T/R	0.1079	likely_benign	0.0969	benign	0.026	Stabilizing	0.017	N	0.383	neutral	N	0.46783389	None	None	N
T/S	0.099	likely_benign	0.1043	benign	-0.354	Destabilizing	None	N	0.096	neutral	N	0.450807917	None	None	N
T/V	0.1054	likely_benign	0.1079	benign	-0.109	Destabilizing	None	N	0.127	neutral	None	None	None	None	N
T/W	0.4838	ambiguous	0.413	ambiguous	-0.913	Destabilizing	0.788	D	0.406	neutral	None	None	None	None	N
T/Y	0.2496	likely_benign	0.2332	benign	-0.578	Destabilizing	0.245	N	0.468	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.