TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32242	96949;96950;96951	chr2:178543249;178543248;178543247	chr2:179407976;179407975;179407974
N2AB	30601	92026;92027;92028	chr2:178543249;178543248;178543247	chr2:179407976;179407975;179407974
N2A	29674	89245;89246;89247	chr2:178543249;178543248;178543247	chr2:179407976;179407975;179407974
N2B	23177	69754;69755;69756	chr2:178543249;178543248;178543247	chr2:179407976;179407975;179407974
Novex-1	23302	70129;70130;70131	chr2:178543249;178543248;178543247	chr2:179407976;179407975;179407974
Novex-2	23369	70330;70331;70332	chr2:178543249;178543248;178543247	chr2:179407976;179407975;179407974
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Fn3-123
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.067
• 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
C/Y	None	None	0.995	N	0.751	0.4	0.750831387573	gnomAD-4.0.0	8.40225E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.18751E-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
C/A	0.3234	likely_benign	0.288	benign	-1.396	Destabilizing	0.702	D	0.533	neutral	None	None	None	None	N
C/D	0.8821	likely_pathogenic	0.8403	pathogenic	-1.056	Destabilizing	0.976	D	0.773	deleterious	None	None	None	None	N
C/E	0.8142	likely_pathogenic	0.7773	pathogenic	-0.81	Destabilizing	0.976	D	0.778	deleterious	None	None	None	None	N
C/F	0.3449	ambiguous	0.2972	benign	-0.882	Destabilizing	0.984	D	0.747	deleterious	N	0.471399718	None	None	N
C/G	0.224	likely_benign	0.1799	benign	-1.754	Destabilizing	0.811	D	0.749	deleterious	N	0.516478647	None	None	N
C/H	0.5486	ambiguous	0.4927	ambiguous	-2.013	Highly Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
C/I	0.6481	likely_pathogenic	0.6093	pathogenic	-0.422	Destabilizing	0.988	D	0.734	prob.delet.	None	None	None	None	N
C/K	0.6483	likely_pathogenic	0.592	pathogenic	-0.5	Destabilizing	0.976	D	0.771	deleterious	None	None	None	None	N
C/L	0.4375	ambiguous	0.3857	ambiguous	-0.422	Destabilizing	0.919	D	0.674	neutral	None	None	None	None	N
C/M	0.5626	ambiguous	0.5372	ambiguous	0.283	Stabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
C/N	0.5766	likely_pathogenic	0.4773	ambiguous	-1.144	Destabilizing	0.976	D	0.777	deleterious	None	None	None	None	N
C/P	0.99	likely_pathogenic	0.9862	pathogenic	-0.726	Destabilizing	0.988	D	0.811	deleterious	None	None	None	None	N
C/Q	0.3933	ambiguous	0.3736	ambiguous	-0.618	Destabilizing	0.988	D	0.817	deleterious	None	None	None	None	N
C/R	0.3001	likely_benign	0.2745	benign	-1.131	Destabilizing	0.968	D	0.813	deleterious	N	0.383873947	None	None	N
C/S	0.2553	likely_benign	0.1992	benign	-1.409	Destabilizing	0.046	N	0.402	neutral	N	0.462950806	None	None	N
C/T	0.5336	ambiguous	0.4672	ambiguous	-0.973	Destabilizing	0.851	D	0.673	neutral	None	None	None	None	N
C/V	0.4879	ambiguous	0.4645	ambiguous	-0.726	Destabilizing	0.919	D	0.707	prob.neutral	None	None	None	None	N
C/W	0.6769	likely_pathogenic	0.6187	pathogenic	-1.278	Destabilizing	0.999	D	0.749	deleterious	N	0.497199453	None	None	N
C/Y	0.4298	ambiguous	0.359	ambiguous	-1.036	Destabilizing	0.995	D	0.751	deleterious	N	0.481827355	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.