TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5476	16651;16652;16653	chr2:178732635;178732634;178732633	chr2:179597362;179597361;179597360
N2AB	5159	15700;15701;15702	chr2:178732635;178732634;178732633	chr2:179597362;179597361;179597360
N2A	4232	12919;12920;12921	chr2:178732635;178732634;178732633	chr2:179597362;179597361;179597360
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-38
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.5413
• Predicted PPI site: I

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
S/T	None	None	0.003	N	0.18	0.157	0.281381271821	gnomAD-4.0.0	8.40227E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.18753E-06	0	0
S/Y	None	None	0.473	N	0.626	0.367	0.647671066071	gnomAD-4.0.0	1.59239E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.88381E-05	0	0	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
S/A	0.1644	likely_benign	0.1597	benign	-0.116	Destabilizing	0.139	N	0.255	neutral	N	0.504563434	None	None	I
S/C	0.3191	likely_benign	0.3128	benign	-0.272	Destabilizing	0.975	D	0.505	neutral	D	0.530096597	None	None	I
S/D	0.6896	likely_pathogenic	0.7441	pathogenic	0.15	Stabilizing	0.704	D	0.339	neutral	None	None	None	None	I
S/E	0.8317	likely_pathogenic	0.8556	pathogenic	0.052	Stabilizing	0.704	D	0.305	neutral	None	None	None	None	I
S/F	0.5169	ambiguous	0.5416	ambiguous	-0.785	Destabilizing	0.006	N	0.381	neutral	N	0.501640559	None	None	I
S/G	0.1671	likely_benign	0.1717	benign	-0.197	Destabilizing	0.495	N	0.337	neutral	None	None	None	None	I
S/H	0.6676	likely_pathogenic	0.6853	pathogenic	-0.559	Destabilizing	0.981	D	0.508	neutral	None	None	None	None	I
S/I	0.5191	ambiguous	0.5491	ambiguous	-0.038	Destabilizing	0.704	D	0.571	neutral	None	None	None	None	I
S/K	0.8787	likely_pathogenic	0.8929	pathogenic	-0.35	Destabilizing	0.704	D	0.319	neutral	None	None	None	None	I
S/L	0.2531	likely_benign	0.2645	benign	-0.038	Destabilizing	0.329	N	0.587	neutral	None	None	None	None	I
S/M	0.4169	ambiguous	0.4333	ambiguous	-0.052	Destabilizing	0.981	D	0.516	neutral	None	None	None	None	I
S/N	0.3133	likely_benign	0.3384	benign	-0.059	Destabilizing	0.704	D	0.355	neutral	None	None	None	None	I
S/P	0.7594	likely_pathogenic	0.8191	pathogenic	-0.037	Destabilizing	0.784	D	0.511	neutral	D	0.534675697	None	None	I
S/Q	0.7756	likely_pathogenic	0.7901	pathogenic	-0.275	Destabilizing	0.944	D	0.437	neutral	None	None	None	None	I
S/R	0.8195	likely_pathogenic	0.8307	pathogenic	-0.119	Destabilizing	0.704	D	0.519	neutral	None	None	None	None	I
S/T	0.0861	likely_benign	0.0917	benign	-0.158	Destabilizing	0.003	N	0.18	neutral	N	0.427353444	None	None	I
S/V	0.4708	ambiguous	0.4901	ambiguous	-0.037	Destabilizing	0.329	N	0.594	neutral	None	None	None	None	I
S/W	0.6349	likely_pathogenic	0.673	pathogenic	-0.87	Destabilizing	0.995	D	0.623	neutral	None	None	None	None	I
S/Y	0.4482	ambiguous	0.4792	ambiguous	-0.544	Destabilizing	0.473	N	0.626	neutral	N	0.502448636	None	None	I

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.