TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6000	18223;18224;18225	chr2:178730535;178730534;178730533	chr2:179595262;179595261;179595260
N2AB	5683	17272;17273;17274	chr2:178730535;178730534;178730533	chr2:179595262;179595261;179595260
N2A	4756	14491;14492;14493	chr2:178730535;178730534;178730533	chr2:179595262;179595261;179595260
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: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-43
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.2449
• 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/D	None	None	None	N	0.091	0.146	0.173771789658	gnomAD-4.0.0	1.59313E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88253E-05	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	0.1982	likely_benign	0.1773	benign	-0.997	Destabilizing	0.016	N	0.573	neutral	None	None	None	None	N
N/C	0.2758	likely_benign	0.2351	benign	-0.019	Destabilizing	0.676	D	0.645	neutral	None	None	None	None	N
N/D	0.1227	likely_benign	0.1237	benign	-0.778	Destabilizing	None	N	0.091	neutral	N	0.358973581	None	None	N
N/E	0.4565	ambiguous	0.4333	ambiguous	-0.677	Destabilizing	0.016	N	0.408	neutral	None	None	None	None	N
N/F	0.5065	ambiguous	0.4916	ambiguous	-0.7	Destabilizing	0.356	N	0.689	prob.neutral	None	None	None	None	N
N/G	0.2867	likely_benign	0.2718	benign	-1.347	Destabilizing	0.016	N	0.402	neutral	None	None	None	None	N
N/H	0.1092	likely_benign	0.1003	benign	-1.046	Destabilizing	0.295	N	0.535	neutral	N	0.499696332	None	None	N
N/I	0.2305	likely_benign	0.211	benign	-0.099	Destabilizing	0.029	N	0.682	prob.neutral	N	0.424545212	None	None	N
N/K	0.4104	ambiguous	0.3801	ambiguous	-0.359	Destabilizing	0.029	N	0.411	neutral	N	0.415346939	None	None	N
N/L	0.2704	likely_benign	0.245	benign	-0.099	Destabilizing	0.038	N	0.645	neutral	None	None	None	None	N
N/M	0.37	ambiguous	0.3392	benign	0.441	Stabilizing	0.356	N	0.639	neutral	None	None	None	None	N
N/P	0.9395	likely_pathogenic	0.943	pathogenic	-0.369	Destabilizing	0.214	N	0.689	prob.neutral	None	None	None	None	N
N/Q	0.3275	likely_benign	0.2985	benign	-0.963	Destabilizing	0.214	N	0.53	neutral	None	None	None	None	N
N/R	0.4064	ambiguous	0.3778	ambiguous	-0.349	Destabilizing	0.214	N	0.53	neutral	None	None	None	None	N
N/S	0.0626	likely_benign	0.0616	benign	-0.987	Destabilizing	None	N	0.096	neutral	N	0.399454767	None	None	N
N/T	0.1326	likely_benign	0.1247	benign	-0.696	Destabilizing	0.012	N	0.411	neutral	N	0.427353444	None	None	N
N/V	0.2376	likely_benign	0.2125	benign	-0.369	Destabilizing	None	N	0.415	neutral	None	None	None	None	N
N/W	0.7977	likely_pathogenic	0.7806	pathogenic	-0.445	Destabilizing	0.864	D	0.703	prob.neutral	None	None	None	None	N
N/Y	0.1874	likely_benign	0.1801	benign	-0.257	Destabilizing	0.295	N	0.664	neutral	N	0.50723838	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.