TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9412	28459;28460;28461	chr2:178710863;178710862;178710861	chr2:179575590;179575589;179575588
N2AB	9095	27508;27509;27510	chr2:178710863;178710862;178710861	chr2:179575590;179575589;179575588
N2A	8168	24727;24728;24729	chr2:178710863;178710862;178710861	chr2:179575590;179575589;179575588
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-80
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.417
• 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
E/G	rs766534072	-0.641	0.549	None	0.395	0.2	0.280181792013	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/G	rs766534072	-0.641	0.549	None	0.395	0.2	0.280181792013	gnomAD-4.0.0	1.36834E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99436E-07	1.15937E-05	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
E/A	0.1339	likely_benign	0.1773	benign	-0.453	Destabilizing	0.201	N	0.351	neutral	None	None	None	None	N
E/C	0.7756	likely_pathogenic	0.8422	pathogenic	-0.027	Destabilizing	0.992	D	0.464	neutral	None	None	None	None	N
E/D	0.0762	likely_benign	0.093	benign	-0.379	Destabilizing	0.001	N	0.147	neutral	None	None	None	None	N
E/F	0.6106	likely_pathogenic	0.6739	pathogenic	-0.299	Destabilizing	0.972	D	0.432	neutral	None	None	None	None	N
E/G	0.1199	likely_benign	0.1696	benign	-0.66	Destabilizing	0.549	D	0.395	neutral	None	None	None	None	N
E/H	0.3245	likely_benign	0.4328	ambiguous	-0.143	Destabilizing	0.972	D	0.305	neutral	None	None	None	None	N
E/I	0.354	ambiguous	0.4434	ambiguous	0.063	Stabilizing	0.92	D	0.439	neutral	None	None	None	None	N
E/K	0.1228	likely_benign	0.1587	benign	0.36	Stabilizing	0.549	D	0.417	neutral	None	None	None	None	N
E/L	0.3493	ambiguous	0.4526	ambiguous	0.063	Stabilizing	0.92	D	0.413	neutral	None	None	None	None	N
E/M	0.3868	ambiguous	0.4749	ambiguous	0.21	Stabilizing	0.992	D	0.407	neutral	None	None	None	None	N
E/N	0.1408	likely_benign	0.1879	benign	-0.021	Destabilizing	0.447	N	0.347	neutral	None	None	None	None	N
E/P	0.7673	likely_pathogenic	0.8407	pathogenic	-0.089	Destabilizing	0.92	D	0.325	neutral	None	None	None	None	N
E/Q	0.1074	likely_benign	0.1471	benign	0.014	Stabilizing	0.549	D	0.411	neutral	None	None	None	None	N
E/R	0.2019	likely_benign	0.2632	benign	0.524	Stabilizing	0.92	D	0.338	neutral	None	None	None	None	N
E/S	0.1288	likely_benign	0.1741	benign	-0.173	Destabilizing	0.059	N	0.254	neutral	None	None	None	None	N
E/T	0.1853	likely_benign	0.2459	benign	0.001	Stabilizing	0.617	D	0.336	neutral	None	None	None	None	N
E/V	0.2127	likely_benign	0.2714	benign	-0.089	Destabilizing	0.896	D	0.39	neutral	None	None	None	None	N
E/W	0.827	likely_pathogenic	0.8755	pathogenic	-0.12	Destabilizing	0.992	D	0.579	neutral	None	None	None	None	N
E/Y	0.4699	ambiguous	0.5399	ambiguous	-0.044	Destabilizing	0.972	D	0.416	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.