TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5675	17248;17249;17250	chr2:178731852;178731851;178731850	chr2:179596579;179596578;179596577
N2AB	5358	16297;16298;16299	chr2:178731852;178731851;178731850	chr2:179596579;179596578;179596577
N2A	4431	13516;13517;13518	chr2:178731852;178731851;178731850	chr2:179596579;179596578;179596577
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-40
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.437
• 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
T/A	rs1198124023	-0.584	0.625	N	0.263	0.254	0.215869574891	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
T/A	rs1198124023	-0.584	0.625	N	0.263	0.254	0.215869574891	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	4.14594E-04	0
T/A	rs1198124023	-0.584	0.625	N	0.263	0.254	0.215869574891	gnomAD-4.0.0	6.19715E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	9.88142E-05	1.60113E-05

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
T/A	0.0666	likely_benign	0.0647	benign	-0.634	Destabilizing	0.625	D	0.263	neutral	N	0.458252354	None	None	N
T/C	0.3209	likely_benign	0.323	benign	-0.389	Destabilizing	0.998	D	0.386	neutral	None	None	None	None	N
T/D	0.3277	likely_benign	0.2965	benign	0.463	Stabilizing	0.728	D	0.357	neutral	None	None	None	None	N
T/E	0.2648	likely_benign	0.2415	benign	0.445	Stabilizing	0.067	N	0.22	neutral	None	None	None	None	N
T/F	0.2059	likely_benign	0.2052	benign	-0.936	Destabilizing	0.991	D	0.421	neutral	None	None	None	None	N
T/G	0.1872	likely_benign	0.1788	benign	-0.834	Destabilizing	0.842	D	0.399	neutral	None	None	None	None	N
T/H	0.1748	likely_benign	0.1673	benign	-0.981	Destabilizing	0.991	D	0.413	neutral	None	None	None	None	N
T/I	0.1213	likely_benign	0.1245	benign	-0.21	Destabilizing	0.966	D	0.365	neutral	N	0.462159451	None	None	N
T/K	0.1543	likely_benign	0.1387	benign	-0.346	Destabilizing	0.002	N	0.16	neutral	N	0.370401296	None	None	N
T/L	0.0948	likely_benign	0.0972	benign	-0.21	Destabilizing	0.842	D	0.332	neutral	None	None	None	None	N
T/M	0.0832	likely_benign	0.0857	benign	-0.158	Destabilizing	0.991	D	0.354	neutral	None	None	None	None	N
T/N	0.0881	likely_benign	0.0833	benign	-0.28	Destabilizing	0.842	D	0.241	neutral	None	None	None	None	N
T/P	0.3695	ambiguous	0.3613	ambiguous	-0.32	Destabilizing	0.891	D	0.393	neutral	N	0.512164197	None	None	N
T/Q	0.1618	likely_benign	0.1562	benign	-0.38	Destabilizing	0.842	D	0.389	neutral	None	None	None	None	N
T/R	0.1293	likely_benign	0.1195	benign	-0.142	Destabilizing	0.012	N	0.217	neutral	N	0.438666516	None	None	N
T/S	0.0907	likely_benign	0.0867	benign	-0.595	Destabilizing	0.625	D	0.297	neutral	N	0.440645241	None	None	N
T/V	0.0995	likely_benign	0.102	benign	-0.32	Destabilizing	0.915	D	0.247	neutral	None	None	None	None	N
T/W	0.5405	ambiguous	0.5338	ambiguous	-0.916	Destabilizing	0.998	D	0.445	neutral	None	None	None	None	N
T/Y	0.2062	likely_benign	0.1965	benign	-0.641	Destabilizing	0.991	D	0.418	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.