TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31658	95197;95198;95199	chr2:178546359;178546358;178546357	chr2:179411086;179411085;179411084
N2AB	30017	90274;90275;90276	chr2:178546359;178546358;178546357	chr2:179411086;179411085;179411084
N2A	29090	87493;87494;87495	chr2:178546359;178546358;178546357	chr2:179411086;179411085;179411084
N2B	22593	68002;68003;68004	chr2:178546359;178546358;178546357	chr2:179411086;179411085;179411084
Novex-1	22718	68377;68378;68379	chr2:178546359;178546358;178546357	chr2:179411086;179411085;179411084
Novex-2	22785	68578;68579;68580	chr2:178546359;178546358;178546357	chr2:179411086;179411085;179411084
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-152
• Domain position: 38
• Structural Position: 70
• Q(SASA): 0.5202
• 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
L/I	rs754798671	-0.111	0.022	N	0.325	0.103	0.167679373172	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
L/I	rs754798671	-0.111	0.022	N	0.325	0.103	0.167679373172	gnomAD-4.0.0	1.59127E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43279E-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
L/A	0.1359	likely_benign	0.1655	benign	-0.54	Destabilizing	0.081	N	0.337	neutral	None	None	None	None	N
L/C	0.3885	ambiguous	0.4287	ambiguous	-0.641	Destabilizing	0.824	D	0.401	neutral	None	None	None	None	N
L/D	0.4528	ambiguous	0.508	ambiguous	-0.095	Destabilizing	0.555	D	0.444	neutral	None	None	None	None	N
L/E	0.291	likely_benign	0.3177	benign	-0.188	Destabilizing	0.38	N	0.423	neutral	None	None	None	None	N
L/F	0.1336	likely_benign	0.1488	benign	-0.604	Destabilizing	0.001	N	0.237	neutral	N	0.498984256	None	None	N
L/G	0.2998	likely_benign	0.349	ambiguous	-0.688	Destabilizing	0.38	N	0.406	neutral	None	None	None	None	N
L/H	0.1961	likely_benign	0.2272	benign	-0.044	Destabilizing	0.915	D	0.442	neutral	N	0.509411893	None	None	N
L/I	0.0808	likely_benign	0.0867	benign	-0.276	Destabilizing	0.022	N	0.325	neutral	N	0.484900238	None	None	N
L/K	0.2388	likely_benign	0.2433	benign	-0.321	Destabilizing	0.38	N	0.396	neutral	None	None	None	None	N
L/M	0.1047	likely_benign	0.1067	benign	-0.404	Destabilizing	0.012	N	0.362	neutral	None	None	None	None	N
L/N	0.2284	likely_benign	0.263	benign	-0.13	Destabilizing	0.555	D	0.436	neutral	None	None	None	None	N
L/P	0.1069	likely_benign	0.1347	benign	-0.332	Destabilizing	None	N	0.296	neutral	N	0.430449677	None	None	N
L/Q	0.1514	likely_benign	0.1719	benign	-0.33	Destabilizing	0.38	N	0.417	neutral	None	None	None	None	N
L/R	0.1805	likely_benign	0.1975	benign	0.181	Stabilizing	0.317	N	0.419	neutral	N	0.479088986	None	None	N
L/S	0.1813	likely_benign	0.2206	benign	-0.566	Destabilizing	0.38	N	0.385	neutral	None	None	None	None	N
L/T	0.1417	likely_benign	0.1646	benign	-0.549	Destabilizing	0.149	N	0.36	neutral	None	None	None	None	N
L/V	0.0749	likely_benign	0.0827	benign	-0.332	Destabilizing	None	N	0.178	neutral	N	0.479262345	None	None	N
L/W	0.2829	likely_benign	0.2976	benign	-0.635	Destabilizing	0.935	D	0.457	neutral	None	None	None	None	N
L/Y	0.2857	likely_benign	0.3083	benign	-0.378	Destabilizing	0.235	N	0.375	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.