TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22124	66595;66596;66597	chr2:178581999;178581998;178581997	chr2:179446726;179446725;179446724
N2AB	20483	61672;61673;61674	chr2:178581999;178581998;178581997	chr2:179446726;179446725;179446724
N2A	19556	58891;58892;58893	chr2:178581999;178581998;178581997	chr2:179446726;179446725;179446724
N2B	13059	39400;39401;39402	chr2:178581999;178581998;178581997	chr2:179446726;179446725;179446724
Novex-1	13184	39775;39776;39777	chr2:178581999;178581998;178581997	chr2:179446726;179446725;179446724
Novex-2	13251	39976;39977;39978	chr2:178581999;178581998;178581997	chr2:179446726;179446725;179446724
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-48
• Domain position: 70
• Structural Position: 102
• Q(SASA): 0.1638
• 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	None	None	0.002	N	0.081	0.123	0.16115917748	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
T/I	rs1449457427	-0.228	0.81	D	0.487	0.325	0.319686207203	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
T/I	rs1449457427	-0.228	0.81	D	0.487	0.325	0.319686207203	gnomAD-4.0.0	2.73759E-06	None	None	None	None	N	None	0	2.23664E-05	None	0	0	None	0	0	1.79935E-06	1.1595E-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
T/A	0.0785	likely_benign	0.0842	benign	-1.037	Destabilizing	0.002	N	0.081	neutral	N	0.454841116	None	None	N
T/C	0.264	likely_benign	0.2774	benign	-0.546	Destabilizing	0.977	D	0.461	neutral	None	None	None	None	N
T/D	0.521	ambiguous	0.5566	ambiguous	-0.644	Destabilizing	0.617	D	0.446	neutral	None	None	None	None	N
T/E	0.4013	ambiguous	0.4358	ambiguous	-0.519	Destabilizing	0.447	N	0.387	neutral	None	None	None	None	N
T/F	0.2735	likely_benign	0.3072	benign	-0.752	Destabilizing	0.92	D	0.497	neutral	None	None	None	None	N
T/G	0.2597	likely_benign	0.2796	benign	-1.408	Destabilizing	0.25	N	0.377	neutral	None	None	None	None	N
T/H	0.2431	likely_benign	0.2675	benign	-1.479	Destabilizing	0.977	D	0.463	neutral	None	None	None	None	N
T/I	0.166	likely_benign	0.1838	benign	-0.092	Destabilizing	0.81	D	0.487	neutral	D	0.522932977	None	None	N
T/K	0.2318	likely_benign	0.2632	benign	-0.622	Destabilizing	0.005	N	0.222	neutral	None	None	None	None	N
T/L	0.1074	likely_benign	0.1176	benign	-0.092	Destabilizing	0.617	D	0.393	neutral	None	None	None	None	N
T/M	0.0896	likely_benign	0.0983	benign	0.003	Stabilizing	0.972	D	0.473	neutral	None	None	None	None	N
T/N	0.1218	likely_benign	0.1236	benign	-0.952	Destabilizing	0.549	D	0.468	neutral	N	0.515313571	None	None	N
T/P	0.7056	likely_pathogenic	0.7104	pathogenic	-0.375	Destabilizing	0.896	D	0.473	neutral	N	0.505221708	None	None	N
T/Q	0.2317	likely_benign	0.2586	benign	-0.858	Destabilizing	0.739	D	0.503	neutral	None	None	None	None	N
T/R	0.1929	likely_benign	0.2165	benign	-0.625	Destabilizing	0.447	N	0.477	neutral	None	None	None	None	N
T/S	0.1123	likely_benign	0.1218	benign	-1.252	Destabilizing	0.02	N	0.085	neutral	N	0.487798896	None	None	N
T/V	0.122	likely_benign	0.1291	benign	-0.375	Destabilizing	0.447	N	0.346	neutral	None	None	None	None	N
T/W	0.6129	likely_pathogenic	0.6591	pathogenic	-0.802	Destabilizing	0.992	D	0.482	neutral	None	None	None	None	N
T/Y	0.2816	likely_benign	0.3066	benign	-0.503	Destabilizing	0.972	D	0.491	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.