TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16414	49465;49466;49467	chr2:178614157;178614156;178614155	chr2:179478884;179478883;179478882
N2AB	14773	44542;44543;44544	chr2:178614157;178614156;178614155	chr2:179478884;179478883;179478882
N2A	13846	41761;41762;41763	chr2:178614157;178614156;178614155	chr2:179478884;179478883;179478882
N2B	7349	22270;22271;22272	chr2:178614157;178614156;178614155	chr2:179478884;179478883;179478882
Novex-1	7474	22645;22646;22647	chr2:178614157;178614156;178614155	chr2:179478884;179478883;179478882
Novex-2	7541	22846;22847;22848	chr2:178614157;178614156;178614155	chr2:179478884;179478883;179478882
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-6
• Domain position: 64
• Structural Position: 96
• Q(SASA): 0.8572
• 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
K/R	rs1329659749	0.272	0.801	N	0.395	0.149	0.28297238246	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/R	rs1329659749	0.272	0.801	N	0.395	0.149	0.28297238246	gnomAD-4.0.0	2.73877E-06	None	None	None	None	N	None	0	4.48209E-05	None	0	0	None	0	0	8.99826E-07	1.15974E-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
K/A	0.4819	ambiguous	0.4708	ambiguous	0.045	Stabilizing	0.688	D	0.375	neutral	None	None	None	None	N
K/C	0.7282	likely_pathogenic	0.7172	pathogenic	-0.368	Destabilizing	0.998	D	0.417	neutral	None	None	None	None	N
K/D	0.6139	likely_pathogenic	0.6141	pathogenic	-0.09	Destabilizing	0.016	N	0.219	neutral	None	None	None	None	N
K/E	0.4054	ambiguous	0.4311	ambiguous	-0.103	Destabilizing	0.454	N	0.347	neutral	N	0.46739332	None	None	N
K/F	0.8873	likely_pathogenic	0.8848	pathogenic	-0.273	Destabilizing	0.991	D	0.447	neutral	None	None	None	None	N
K/G	0.4329	ambiguous	0.4225	ambiguous	-0.093	Destabilizing	0.002	N	0.184	neutral	None	None	None	None	N
K/H	0.2768	likely_benign	0.2769	benign	-0.205	Destabilizing	0.974	D	0.435	neutral	None	None	None	None	N
K/I	0.7504	likely_pathogenic	0.7507	pathogenic	0.323	Stabilizing	0.966	D	0.467	neutral	D	0.564613887	None	None	N
K/L	0.6152	likely_pathogenic	0.6035	pathogenic	0.323	Stabilizing	0.915	D	0.455	neutral	None	None	None	None	N
K/M	0.4737	ambiguous	0.465	ambiguous	0.03	Stabilizing	0.998	D	0.425	neutral	None	None	None	None	N
K/N	0.4106	ambiguous	0.3981	ambiguous	0.128	Stabilizing	0.005	N	0.135	neutral	N	0.439154313	None	None	N
K/P	0.9086	likely_pathogenic	0.9145	pathogenic	0.255	Stabilizing	0.991	D	0.455	neutral	None	None	None	None	N
K/Q	0.2027	likely_benign	0.2056	benign	-0.035	Destabilizing	0.891	D	0.397	neutral	N	0.456655395	None	None	N
K/R	0.0834	likely_benign	0.0874	benign	-0.013	Destabilizing	0.801	D	0.395	neutral	N	0.466193887	None	None	N
K/S	0.4683	ambiguous	0.4559	ambiguous	-0.296	Destabilizing	0.525	D	0.325	neutral	None	None	None	None	N
K/T	0.3738	ambiguous	0.3603	ambiguous	-0.184	Destabilizing	0.801	D	0.445	neutral	N	0.513576123	None	None	N
K/V	0.6401	likely_pathogenic	0.6451	pathogenic	0.255	Stabilizing	0.915	D	0.461	neutral	None	None	None	None	N
K/W	0.8621	likely_pathogenic	0.8731	pathogenic	-0.344	Destabilizing	0.998	D	0.474	neutral	None	None	None	None	N
K/Y	0.6982	likely_pathogenic	0.7025	pathogenic	0.015	Stabilizing	0.991	D	0.437	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.