TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32501	97726;97727;97728	chr2:178541576;178541575;178541574	chr2:179406303;179406302;179406301
N2AB	30860	92803;92804;92805	chr2:178541576;178541575;178541574	chr2:179406303;179406302;179406301
N2A	29933	90022;90023;90024	chr2:178541576;178541575;178541574	chr2:179406303;179406302;179406301
N2B	23436	70531;70532;70533	chr2:178541576;178541575;178541574	chr2:179406303;179406302;179406301
Novex-1	23561	70906;70907;70908	chr2:178541576;178541575;178541574	chr2:179406303;179406302;179406301
Novex-2	23628	71107;71108;71109	chr2:178541576;178541575;178541574	chr2:179406303;179406302;179406301
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-125
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.2243
• 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
G/E	rs1694532361	None	0.997	N	0.761	0.38	0.430923071578	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
G/R	None	None	0.999	N	0.837	0.449	0.563173181975	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

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	0.2499	likely_benign	0.1977	benign	-0.822	Destabilizing	0.995	D	0.686	prob.neutral	N	0.496852872	None	None	N
G/C	0.4763	ambiguous	0.4003	ambiguous	-1.168	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
G/D	0.5129	ambiguous	0.4828	ambiguous	-1.825	Destabilizing	0.669	D	0.556	neutral	None	None	None	None	N
G/E	0.5398	ambiguous	0.4689	ambiguous	-1.893	Destabilizing	0.997	D	0.761	deleterious	N	0.507359804	None	None	N
G/F	0.8323	likely_pathogenic	0.7875	pathogenic	-1.23	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
G/H	0.7601	likely_pathogenic	0.7049	pathogenic	-1.384	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
G/I	0.7525	likely_pathogenic	0.6443	pathogenic	-0.505	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
G/K	0.7578	likely_pathogenic	0.6832	pathogenic	-1.371	Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
G/L	0.6973	likely_pathogenic	0.6028	pathogenic	-0.505	Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	N
G/M	0.7922	likely_pathogenic	0.7086	pathogenic	-0.45	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
G/N	0.6058	likely_pathogenic	0.5305	ambiguous	-1.113	Destabilizing	0.998	D	0.78	deleterious	None	None	None	None	N
G/P	0.9772	likely_pathogenic	0.9618	pathogenic	-0.572	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
G/Q	0.6785	likely_pathogenic	0.5971	pathogenic	-1.364	Destabilizing	0.999	D	0.842	deleterious	None	None	None	None	N
G/R	0.671	likely_pathogenic	0.6096	pathogenic	-1.004	Destabilizing	0.999	D	0.837	deleterious	N	0.508880741	None	None	N
G/S	0.1559	likely_benign	0.1379	benign	-1.279	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
G/T	0.4156	ambiguous	0.3285	benign	-1.285	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
G/V	0.6373	likely_pathogenic	0.5274	ambiguous	-0.572	Destabilizing	0.999	D	0.835	deleterious	N	0.505121759	None	None	N
G/W	0.7892	likely_pathogenic	0.7619	pathogenic	-1.551	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
G/Y	0.7508	likely_pathogenic	0.6988	pathogenic	-1.164	Destabilizing	1.0	D	0.841	deleterious	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.