TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17157	51694;51695;51696	chr2:178609954;178609953;178609952	chr2:179474681;179474680;179474679
N2AB	15516	46771;46772;46773	chr2:178609954;178609953;178609952	chr2:179474681;179474680;179474679
N2A	14589	43990;43991;43992	chr2:178609954;178609953;178609952	chr2:179474681;179474680;179474679
N2B	8092	24499;24500;24501	chr2:178609954;178609953;178609952	chr2:179474681;179474680;179474679
Novex-1	8217	24874;24875;24876	chr2:178609954;178609953;178609952	chr2:179474681;179474680;179474679
Novex-2	8284	25075;25076;25077	chr2:178609954;178609953;178609952	chr2:179474681;179474680;179474679
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: Fn3-13
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.5741
• 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/D	None	None	0.999	N	0.552	0.406	0.33110744837	gnomAD-4.0.0	6.84676E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99913E-07	0	0
H/R	None	None	0.999	N	0.483	0.272	0.319970858106	gnomAD-4.0.0	1.3693E-06	None	None	None	None	N	None	5.98767E-05	0	None	0	0	None	0	0	0	0	0
H/Y	None	None	0.4	N	0.243	0.245	0.238096912614	gnomAD-4.0.0	3.42338E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79983E-06	1.16031E-05	3.31664E-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
H/A	0.4257	ambiguous	0.4252	ambiguous	0.068	Stabilizing	0.993	D	0.549	neutral	None	None	None	None	N
H/C	0.2359	likely_benign	0.218	benign	0.73	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
H/D	0.4199	ambiguous	0.4098	ambiguous	-0.068	Destabilizing	0.999	D	0.552	neutral	N	0.436324352	None	None	N
H/E	0.4272	ambiguous	0.3978	ambiguous	-0.026	Destabilizing	0.998	D	0.491	neutral	None	None	None	None	N
H/F	0.3807	ambiguous	0.3146	benign	0.817	Stabilizing	0.991	D	0.55	neutral	None	None	None	None	N
H/G	0.5016	ambiguous	0.5001	ambiguous	-0.249	Destabilizing	0.998	D	0.546	neutral	None	None	None	None	N
H/I	0.3574	ambiguous	0.3238	benign	0.897	Stabilizing	0.998	D	0.679	prob.neutral	None	None	None	None	N
H/K	0.3187	likely_benign	0.2966	benign	0.008	Stabilizing	0.998	D	0.539	neutral	None	None	None	None	N
H/L	0.1497	likely_benign	0.1336	benign	0.897	Stabilizing	0.98	D	0.569	neutral	N	0.3921495	None	None	N
H/M	0.4672	ambiguous	0.4598	ambiguous	0.734	Stabilizing	1.0	D	0.664	neutral	None	None	None	None	N
H/N	0.1697	likely_benign	0.1697	benign	0.099	Stabilizing	0.997	D	0.516	neutral	N	0.457585059	None	None	N
H/P	0.7657	likely_pathogenic	0.7593	pathogenic	0.646	Stabilizing	0.999	D	0.663	neutral	N	0.42847566	None	None	N
H/Q	0.2326	likely_benign	0.2216	benign	0.251	Stabilizing	0.999	D	0.507	neutral	N	0.445194551	None	None	N
H/R	0.1488	likely_benign	0.1344	benign	-0.652	Destabilizing	0.999	D	0.483	neutral	N	0.452581884	None	None	N
H/S	0.3227	likely_benign	0.329	benign	0.203	Stabilizing	0.993	D	0.554	neutral	None	None	None	None	N
H/T	0.338	likely_benign	0.3405	ambiguous	0.342	Stabilizing	0.998	D	0.587	neutral	None	None	None	None	N
H/V	0.2907	likely_benign	0.2713	benign	0.646	Stabilizing	0.996	D	0.59	neutral	None	None	None	None	N
H/W	0.4702	ambiguous	0.4204	ambiguous	0.855	Stabilizing	1.0	D	0.671	neutral	None	None	None	None	N
H/Y	0.1476	likely_benign	0.1169	benign	1.123	Stabilizing	0.4	N	0.243	neutral	N	0.472650512	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.