TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18393	55402;55403;55404	chr2:178602094;178602093;178602092	chr2:179466821;179466820;179466819
N2AB	16752	50479;50480;50481	chr2:178602094;178602093;178602092	chr2:179466821;179466820;179466819
N2A	15825	47698;47699;47700	chr2:178602094;178602093;178602092	chr2:179466821;179466820;179466819
N2B	9328	28207;28208;28209	chr2:178602094;178602093;178602092	chr2:179466821;179466820;179466819
Novex-1	9453	28582;28583;28584	chr2:178602094;178602093;178602092	chr2:179466821;179466820;179466819
Novex-2	9520	28783;28784;28785	chr2:178602094;178602093;178602092	chr2:179466821;179466820;179466819
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-115
• Domain position: 12
• Structural Position: 24
• Q(SASA): 0.2558
• Predicted PPI site: I

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
G/S	rs2053610320	None	1.0	D	0.855	0.628	0.696735452351	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	2.07125E-04	0
G/S	rs2053610320	None	1.0	D	0.855	0.628	0.696735452351	gnomAD-4.0.0	6.58068E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.07125E-04	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
G/A	0.4583	ambiguous	0.4585	ambiguous	-0.238	Destabilizing	1.0	D	0.751	deleterious	D	0.587143952	None	None	I
G/C	0.5856	likely_pathogenic	0.5962	pathogenic	-0.794	Destabilizing	1.0	D	0.835	deleterious	D	0.587749365	None	None	I
G/D	0.4389	ambiguous	0.4567	ambiguous	-0.778	Destabilizing	1.0	D	0.871	deleterious	D	0.548151009	None	None	I
G/E	0.5879	likely_pathogenic	0.6162	pathogenic	-0.959	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
G/F	0.9065	likely_pathogenic	0.9017	pathogenic	-1.113	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	I
G/H	0.6856	likely_pathogenic	0.7016	pathogenic	-0.437	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	I
G/I	0.9207	likely_pathogenic	0.9233	pathogenic	-0.483	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	I
G/K	0.683	likely_pathogenic	0.7178	pathogenic	-0.667	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	I
G/L	0.8671	likely_pathogenic	0.8572	pathogenic	-0.483	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
G/M	0.8844	likely_pathogenic	0.8776	pathogenic	-0.376	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
G/N	0.4603	ambiguous	0.4365	ambiguous	-0.336	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	I
G/P	0.9834	likely_pathogenic	0.9847	pathogenic	-0.372	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	I
G/Q	0.596	likely_pathogenic	0.6244	pathogenic	-0.687	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	I
G/R	0.5787	likely_pathogenic	0.6328	pathogenic	-0.172	Destabilizing	1.0	D	0.879	deleterious	D	0.603365117	None	None	I
G/S	0.2571	likely_benign	0.2559	benign	-0.421	Destabilizing	1.0	D	0.855	deleterious	D	0.586942148	None	None	I
G/T	0.6183	likely_pathogenic	0.6014	pathogenic	-0.547	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	I
G/V	0.8445	likely_pathogenic	0.849	pathogenic	-0.372	Destabilizing	1.0	D	0.841	deleterious	D	0.603566922	None	None	I
G/W	0.8463	likely_pathogenic	0.8697	pathogenic	-1.226	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
G/Y	0.8316	likely_pathogenic	0.831	pathogenic	-0.883	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	I

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.