TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5958	18097;18098;18099	chr2:178730661;178730660;178730659	chr2:179595388;179595387;179595386
N2AB	5641	17146;17147;17148	chr2:178730661;178730660;178730659	chr2:179595388;179595387;179595386
N2A	4714	14365;14366;14367	chr2:178730661;178730660;178730659	chr2:179595388;179595387;179595386
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-43
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.5179
• 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	rs2080287202	None	0.999	N	0.498	0.228	0.349870743963	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/D	rs2080287202	None	0.999	N	0.498	0.228	0.349870743963	gnomAD-4.0.0	4.95792E-06	None	None	None	None	N	None	1.33508E-05	0	None	0	0	None	0	0	5.93363E-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
E/A	0.1679	likely_benign	0.1321	benign	-0.499	Destabilizing	0.999	D	0.67	neutral	N	0.490758893	None	None	N
E/C	0.9255	likely_pathogenic	0.8755	pathogenic	-0.341	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
E/D	0.3346	likely_benign	0.312	benign	-0.516	Destabilizing	0.999	D	0.498	neutral	N	0.484060168	None	None	N
E/F	0.8923	likely_pathogenic	0.8403	pathogenic	0.083	Stabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
E/G	0.3364	likely_benign	0.2898	benign	-0.778	Destabilizing	1.0	D	0.665	neutral	N	0.506193802	None	None	N
E/H	0.6879	likely_pathogenic	0.6139	pathogenic	0.355	Stabilizing	1.0	D	0.645	neutral	None	None	None	None	N
E/I	0.3897	ambiguous	0.2915	benign	0.235	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
E/K	0.1637	likely_benign	0.1394	benign	0.17	Stabilizing	0.999	D	0.646	neutral	D	0.534635625	None	None	N
E/L	0.4011	ambiguous	0.3139	benign	0.235	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
E/M	0.4677	ambiguous	0.3644	ambiguous	0.238	Stabilizing	1.0	D	0.666	neutral	None	None	None	None	N
E/N	0.4753	ambiguous	0.4128	ambiguous	-0.515	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
E/P	0.3412	ambiguous	0.2995	benign	0.012	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
E/Q	0.1695	likely_benign	0.1472	benign	-0.399	Destabilizing	1.0	D	0.603	neutral	N	0.486884552	None	None	N
E/R	0.3568	ambiguous	0.3009	benign	0.55	Stabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
E/S	0.4313	ambiguous	0.3682	ambiguous	-0.669	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
E/T	0.383	ambiguous	0.3015	benign	-0.422	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
E/V	0.2282	likely_benign	0.1692	benign	0.012	Stabilizing	1.0	D	0.72	prob.delet.	N	0.488481168	None	None	N
E/W	0.9702	likely_pathogenic	0.9506	pathogenic	0.375	Stabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
E/Y	0.83	likely_pathogenic	0.7664	pathogenic	0.365	Stabilizing	1.0	D	0.685	prob.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.