TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27329	82210;82211;82212	chr2:178564147;178564146;178564145	chr2:179428874;179428873;179428872
N2AB	25688	77287;77288;77289	chr2:178564147;178564146;178564145	chr2:179428874;179428873;179428872
N2A	24761	74506;74507;74508	chr2:178564147;178564146;178564145	chr2:179428874;179428873;179428872
N2B	18264	55015;55016;55017	chr2:178564147;178564146;178564145	chr2:179428874;179428873;179428872
Novex-1	18389	55390;55391;55392	chr2:178564147;178564146;178564145	chr2:179428874;179428873;179428872
Novex-2	18456	55591;55592;55593	chr2:178564147;178564146;178564145	chr2:179428874;179428873;179428872
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-140
• Domain position: 52
• Structural Position: 131
• Q(SASA): 0.8052
• 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
I/V	None	None	0.012	N	0.195	0.067	0.0846915920261	gnomAD-4.0.0	4.78953E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29641E-06	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
I/A	0.1939	likely_benign	0.1734	benign	-0.517	Destabilizing	0.067	N	0.339	neutral	None	None	None	None	N
I/C	0.5886	likely_pathogenic	0.5475	ambiguous	-0.692	Destabilizing	0.935	D	0.237	neutral	None	None	None	None	N
I/D	0.4007	ambiguous	0.3569	ambiguous	-0.273	Destabilizing	0.791	D	0.299	neutral	None	None	None	None	N
I/E	0.3352	likely_benign	0.3054	benign	-0.362	Destabilizing	0.555	D	0.325	neutral	None	None	None	None	N
I/F	0.1053	likely_benign	0.1009	benign	-0.6	Destabilizing	None	N	0.171	neutral	N	0.466481396	None	None	N
I/G	0.4154	ambiguous	0.3708	ambiguous	-0.652	Destabilizing	0.555	D	0.347	neutral	None	None	None	None	N
I/H	0.3355	likely_benign	0.3089	benign	0.031	Stabilizing	0.935	D	0.245	neutral	None	None	None	None	N
I/K	0.2777	likely_benign	0.2624	benign	-0.356	Destabilizing	0.555	D	0.337	neutral	None	None	None	None	N
I/L	0.0666	likely_benign	0.0591	benign	-0.284	Destabilizing	None	N	0.133	neutral	N	0.407395807	None	None	N
I/M	0.0878	likely_benign	0.0821	benign	-0.508	Destabilizing	0.012	N	0.166	neutral	N	0.477602466	None	None	N
I/N	0.1611	likely_benign	0.1536	benign	-0.202	Destabilizing	0.741	D	0.287	neutral	N	0.409067888	None	None	N
I/P	0.2912	likely_benign	0.2516	benign	-0.331	Destabilizing	0.791	D	0.287	neutral	None	None	None	None	N
I/Q	0.2817	likely_benign	0.2602	benign	-0.397	Destabilizing	0.555	D	0.275	neutral	None	None	None	None	N
I/R	0.2097	likely_benign	0.1994	benign	0.154	Stabilizing	0.555	D	0.297	neutral	None	None	None	None	N
I/S	0.1705	likely_benign	0.1649	benign	-0.594	Destabilizing	0.211	N	0.359	neutral	N	0.416089861	None	None	N
I/T	0.1701	likely_benign	0.1498	benign	-0.577	Destabilizing	0.117	N	0.312	neutral	N	0.447279559	None	None	N
I/V	0.0745	likely_benign	0.0694	benign	-0.331	Destabilizing	0.012	N	0.195	neutral	N	0.431811462	None	None	N
I/W	0.5353	ambiguous	0.5098	ambiguous	-0.63	Destabilizing	0.935	D	0.255	neutral	None	None	None	None	N
I/Y	0.317	likely_benign	0.3033	benign	-0.384	Destabilizing	0.235	N	0.333	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.