TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29461	88606;88607;88608	chr2:178555078;178555077;178555076	chr2:179419805;179419804;179419803
N2AB	27820	83683;83684;83685	chr2:178555078;178555077;178555076	chr2:179419805;179419804;179419803
N2A	26893	80902;80903;80904	chr2:178555078;178555077;178555076	chr2:179419805;179419804;179419803
N2B	20396	61411;61412;61413	chr2:178555078;178555077;178555076	chr2:179419805;179419804;179419803
Novex-1	20521	61786;61787;61788	chr2:178555078;178555077;178555076	chr2:179419805;179419804;179419803
Novex-2	20588	61987;61988;61989	chr2:178555078;178555077;178555076	chr2:179419805;179419804;179419803
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-146
• Domain position: 18
• Structural Position: 31
• Q(SASA): 0.456
• 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
R/T	None	None	0.801	N	0.505	0.269	0.388970301349	gnomAD-4.0.0	2.40067E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62503E-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
R/A	0.3099	likely_benign	0.2804	benign	-0.35	Destabilizing	0.688	D	0.516	neutral	None	None	None	None	N
R/C	0.1439	likely_benign	0.1421	benign	-0.444	Destabilizing	0.998	D	0.573	neutral	None	None	None	None	N
R/D	0.6303	likely_pathogenic	0.5927	pathogenic	0.096	Stabilizing	0.842	D	0.545	neutral	None	None	None	None	N
R/E	0.3001	likely_benign	0.2806	benign	0.196	Stabilizing	0.525	D	0.478	neutral	None	None	None	None	N
R/F	0.4542	ambiguous	0.4065	ambiguous	-0.412	Destabilizing	0.991	D	0.595	neutral	None	None	None	None	N
R/G	0.2643	likely_benign	0.2401	benign	-0.601	Destabilizing	0.801	D	0.547	neutral	N	0.493135719	None	None	N
R/H	0.0967	likely_benign	0.093	benign	-1.023	Destabilizing	0.991	D	0.538	neutral	None	None	None	None	N
R/I	0.1905	likely_benign	0.177	benign	0.295	Stabilizing	0.966	D	0.599	neutral	N	0.493482436	None	None	N
R/K	0.0912	likely_benign	0.0897	benign	-0.317	Destabilizing	0.002	N	0.179	neutral	N	0.409517045	None	None	N
R/L	0.1875	likely_benign	0.168	benign	0.295	Stabilizing	0.842	D	0.547	neutral	None	None	None	None	N
R/M	0.1946	likely_benign	0.1846	benign	-0.139	Destabilizing	0.991	D	0.573	neutral	None	None	None	None	N
R/N	0.4966	ambiguous	0.4579	ambiguous	None	Stabilizing	0.842	D	0.435	neutral	None	None	None	None	N
R/P	0.742	likely_pathogenic	0.7105	pathogenic	0.101	Stabilizing	0.915	D	0.594	neutral	None	None	None	None	N
R/Q	0.0928	likely_benign	0.0913	benign	-0.115	Destabilizing	0.842	D	0.441	neutral	None	None	None	None	N
R/S	0.3699	ambiguous	0.3315	benign	-0.585	Destabilizing	0.625	D	0.515	neutral	N	0.437261007	None	None	N
R/T	0.1499	likely_benign	0.1378	benign	-0.319	Destabilizing	0.801	D	0.505	neutral	N	0.440511955	None	None	N
R/V	0.2467	likely_benign	0.2263	benign	0.101	Stabilizing	0.915	D	0.573	neutral	None	None	None	None	N
R/W	0.1668	likely_benign	0.159	benign	-0.29	Destabilizing	0.998	D	0.587	neutral	None	None	None	None	N
R/Y	0.3413	ambiguous	0.3028	benign	0.076	Stabilizing	0.991	D	0.589	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.