TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14814	44665;44666;44667	chr2:178625381;178625380;178625379	chr2:179490108;179490107;179490106
N2AB	13173	39742;39743;39744	chr2:178625381;178625380;178625379	chr2:179490108;179490107;179490106
N2A	12246	36961;36962;36963	chr2:178625381;178625380;178625379	chr2:179490108;179490107;179490106
N2B	5749	17470;17471;17472	chr2:178625381;178625380;178625379	chr2:179490108;179490107;179490106
Novex-1	5874	17845;17846;17847	chr2:178625381;178625380;178625379	chr2:179490108;179490107;179490106
Novex-2	5941	18046;18047;18048	chr2:178625381;178625380;178625379	chr2:179490108;179490107;179490106
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-99
• Domain position: 50
• Structural Position: 130
• Q(SASA): 0.5492
• 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/D	None	None	None	N	0.174	0.05	0.288727942641	gnomAD-4.0.0	6.99536E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.09182E-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
E/A	0.172	likely_benign	0.2037	benign	-0.049	Destabilizing	0.004	N	0.221	neutral	D	0.537882055	None	None	N
E/C	0.8762	likely_pathogenic	0.9084	pathogenic	-0.046	Destabilizing	0.968	D	0.495	neutral	None	None	None	None	N
E/D	0.1317	likely_benign	0.1522	benign	-0.264	Destabilizing	None	N	0.174	neutral	N	0.501054178	None	None	N
E/F	0.7039	likely_pathogenic	0.7752	pathogenic	-0.072	Destabilizing	0.726	D	0.464	neutral	None	None	None	None	N
E/G	0.229	likely_benign	0.2812	benign	-0.166	Destabilizing	0.22	N	0.379	neutral	D	0.553226759	None	None	N
E/H	0.476	ambiguous	0.509	ambiguous	0.406	Stabilizing	0.909	D	0.305	neutral	None	None	None	None	N
E/I	0.3309	likely_benign	0.406	ambiguous	0.204	Stabilizing	0.396	N	0.412	neutral	None	None	None	None	N
E/K	0.1601	likely_benign	0.1845	benign	0.535	Stabilizing	0.22	N	0.339	neutral	N	0.510270083	None	None	N
E/L	0.4499	ambiguous	0.5197	ambiguous	0.204	Stabilizing	0.157	N	0.436	neutral	None	None	None	None	N
E/M	0.4691	ambiguous	0.5441	ambiguous	0.089	Stabilizing	0.909	D	0.431	neutral	None	None	None	None	N
E/N	0.2779	likely_benign	0.3343	benign	0.24	Stabilizing	0.396	N	0.287	neutral	None	None	None	None	N
E/P	0.8104	likely_pathogenic	0.8734	pathogenic	0.138	Stabilizing	0.726	D	0.33	neutral	None	None	None	None	N
E/Q	0.1651	likely_benign	0.1721	benign	0.264	Stabilizing	0.497	N	0.327	neutral	N	0.514099582	None	None	N
E/R	0.2578	likely_benign	0.2935	benign	0.675	Stabilizing	0.567	D	0.313	neutral	None	None	None	None	N
E/S	0.2178	likely_benign	0.2441	benign	0.133	Stabilizing	0.157	N	0.323	neutral	None	None	None	None	N
E/T	0.2398	likely_benign	0.2835	benign	0.242	Stabilizing	0.272	N	0.344	neutral	None	None	None	None	N
E/V	0.1965	likely_benign	0.2347	benign	0.138	Stabilizing	0.009	N	0.261	neutral	N	0.51692493	None	None	N
E/W	0.8775	likely_pathogenic	0.9149	pathogenic	-0.018	Destabilizing	0.968	D	0.583	neutral	None	None	None	None	N
E/Y	0.6189	likely_pathogenic	0.7015	pathogenic	0.151	Stabilizing	0.89	D	0.431	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.