TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19986	60181;60182;60183	chr2:178591863;178591862;178591861	chr2:179456590;179456589;179456588
N2AB	18345	55258;55259;55260	chr2:178591863;178591862;178591861	chr2:179456590;179456589;179456588
N2A	17418	52477;52478;52479	chr2:178591863;178591862;178591861	chr2:179456590;179456589;179456588
N2B	10921	32986;32987;32988	chr2:178591863;178591862;178591861	chr2:179456590;179456589;179456588
Novex-1	11046	33361;33362;33363	chr2:178591863;178591862;178591861	chr2:179456590;179456589;179456588
Novex-2	11113	33562;33563;33564	chr2:178591863;178591862;178591861	chr2:179456590;179456589;179456588
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-33
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.2715
• 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
H/L	None	None	0.997	N	0.773	0.374	0.476598743245	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
H/R	None	None	0.999	N	0.555	0.381	0.315609569513	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25001E-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
H/A	0.737	likely_pathogenic	0.6653	pathogenic	-0.841	Destabilizing	0.985	D	0.669	neutral	None	None	None	None	N
H/C	0.4108	ambiguous	0.4144	ambiguous	0.046	Stabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
H/D	0.8658	likely_pathogenic	0.819	pathogenic	-1.126	Destabilizing	0.99	D	0.641	neutral	N	0.485945096	None	None	N
H/E	0.8853	likely_pathogenic	0.8517	pathogenic	-0.992	Destabilizing	0.993	D	0.517	neutral	None	None	None	None	N
H/F	0.5376	ambiguous	0.5262	ambiguous	0.716	Stabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	N
H/G	0.898	likely_pathogenic	0.8743	pathogenic	-1.244	Destabilizing	0.993	D	0.703	prob.neutral	None	None	None	None	N
H/I	0.5652	likely_pathogenic	0.5242	ambiguous	0.303	Stabilizing	0.999	D	0.839	deleterious	None	None	None	None	N
H/K	0.8958	likely_pathogenic	0.8707	pathogenic	-0.54	Destabilizing	0.993	D	0.638	neutral	None	None	None	None	N
H/L	0.3573	ambiguous	0.3326	benign	0.303	Stabilizing	0.997	D	0.773	deleterious	N	0.361421162	None	None	N
H/M	0.7806	likely_pathogenic	0.7722	pathogenic	0.092	Stabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
H/N	0.5126	ambiguous	0.425	ambiguous	-0.881	Destabilizing	0.997	D	0.547	neutral	N	0.49671945	None	None	N
H/P	0.3045	likely_benign	0.2439	benign	-0.06	Destabilizing	0.135	N	0.45	neutral	N	0.446175986	None	None	N
H/Q	0.7621	likely_pathogenic	0.6983	pathogenic	-0.59	Destabilizing	0.999	D	0.561	neutral	N	0.477613614	None	None	N
H/R	0.6878	likely_pathogenic	0.6263	pathogenic	-1.209	Destabilizing	0.999	D	0.555	neutral	N	0.515227853	None	None	N
H/S	0.7324	likely_pathogenic	0.6675	pathogenic	-0.756	Destabilizing	0.993	D	0.661	neutral	None	None	None	None	N
H/T	0.7653	likely_pathogenic	0.7002	pathogenic	-0.505	Destabilizing	0.998	D	0.737	prob.delet.	None	None	None	None	N
H/V	0.5092	ambiguous	0.4766	ambiguous	-0.06	Destabilizing	0.998	D	0.802	deleterious	None	None	None	None	N
H/W	0.5965	likely_pathogenic	0.6143	pathogenic	1.071	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
H/Y	0.2393	likely_benign	0.2206	benign	1.012	Stabilizing	0.999	D	0.539	neutral	N	0.444290474	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.