TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15928	48007;48008;48009	chr2:178617213;178617212;178617211	chr2:179481940;179481939;179481938
N2AB	14287	43084;43085;43086	chr2:178617213;178617212;178617211	chr2:179481940;179481939;179481938
N2A	13360	40303;40304;40305	chr2:178617213;178617212;178617211	chr2:179481940;179481939;179481938
N2B	6863	20812;20813;20814	chr2:178617213;178617212;178617211	chr2:179481940;179481939;179481938
Novex-1	6988	21187;21188;21189	chr2:178617213;178617212;178617211	chr2:179481940;179481939;179481938
Novex-2	7055	21388;21389;21390	chr2:178617213;178617212;178617211	chr2:179481940;179481939;179481938
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-3
• Domain position: 70
• Structural Position: 102
• Q(SASA): 0.2054
• 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
N/H	rs1442489406	-1.116	0.794	N	0.407	0.184	0.270001397563	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	1.18203E-03	None	0	0	None	0	None	0	0	0
N/H	rs1442489406	-1.116	0.794	N	0.407	0.184	0.270001397563	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
N/H	rs1442489406	-1.116	0.794	N	0.407	0.184	0.270001397563	gnomAD-4.0.0	6.58129E-06	None	None	None	None	N	None	0	6.55996E-05	None	0	0	None	0	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
N/A	0.1306	likely_benign	0.1445	benign	-0.946	Destabilizing	0.001	N	0.185	neutral	None	None	None	None	N
N/C	0.149	likely_benign	0.1605	benign	-0.024	Destabilizing	0.951	D	0.485	neutral	None	None	None	None	N
N/D	0.1588	likely_benign	0.2184	benign	-0.638	Destabilizing	0.183	N	0.295	neutral	N	0.4533678	None	None	N
N/E	0.1998	likely_benign	0.2303	benign	-0.537	Destabilizing	0.129	N	0.279	neutral	None	None	None	None	N
N/F	0.3584	ambiguous	0.4129	ambiguous	-0.687	Destabilizing	0.836	D	0.501	neutral	None	None	None	None	N
N/G	0.1974	likely_benign	0.2326	benign	-1.295	Destabilizing	0.129	N	0.277	neutral	None	None	None	None	N
N/H	0.0839	likely_benign	0.0918	benign	-1.017	Destabilizing	0.794	D	0.407	neutral	N	0.443061622	None	None	N
N/I	0.1258	likely_benign	0.1351	benign	-0.055	Destabilizing	0.655	D	0.525	neutral	N	0.461722907	None	None	N
N/K	0.099	likely_benign	0.0989	benign	-0.345	Destabilizing	0.001	N	0.087	neutral	N	0.377786949	None	None	N
N/L	0.1704	likely_benign	0.1811	benign	-0.055	Destabilizing	0.418	N	0.401	neutral	None	None	None	None	N
N/M	0.2011	likely_benign	0.2196	benign	0.416	Stabilizing	0.94	D	0.455	neutral	None	None	None	None	N
N/P	0.8144	likely_pathogenic	0.8282	pathogenic	-0.323	Destabilizing	0.593	D	0.449	neutral	None	None	None	None	N
N/Q	0.139	likely_benign	0.1492	benign	-0.934	Destabilizing	0.264	N	0.394	neutral	None	None	None	None	N
N/R	0.1271	likely_benign	0.1232	benign	-0.371	Destabilizing	0.264	N	0.333	neutral	None	None	None	None	N
N/S	0.078	likely_benign	0.0838	benign	-0.977	Destabilizing	0.003	N	0.068	neutral	N	0.371622601	None	None	N
N/T	0.0923	likely_benign	0.1	benign	-0.681	Destabilizing	0.007	N	0.113	neutral	N	0.337487403	None	None	N
N/V	0.1228	likely_benign	0.1345	benign	-0.323	Destabilizing	0.264	N	0.426	neutral	None	None	None	None	N
N/W	0.5979	likely_pathogenic	0.6535	pathogenic	-0.449	Destabilizing	0.983	D	0.521	neutral	None	None	None	None	N
N/Y	0.1274	likely_benign	0.1491	benign	-0.251	Destabilizing	0.921	D	0.458	neutral	N	0.481992935	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.