TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8981	27166;27167;27168	chr2:178713193;178713192;178713191	chr2:179577920;179577919;179577918
N2AB	8664	26215;26216;26217	chr2:178713193;178713192;178713191	chr2:179577920;179577919;179577918
N2A	7737	23434;23435;23436	chr2:178713193;178713192;178713191	chr2:179577920;179577919;179577918
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-75
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.1371
• 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	0.681	N	0.793	0.245	0.56524285216	gnomAD-4.0.0	1.20033E-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
C/A	0.5208	ambiguous	0.5742	pathogenic	-1.684	Destabilizing	0.25	N	0.652	neutral	None	None	None	None	N
C/D	0.9924	likely_pathogenic	0.9964	pathogenic	-1.618	Destabilizing	0.85	D	0.803	deleterious	None	None	None	None	N
C/E	0.9952	likely_pathogenic	0.9974	pathogenic	-1.409	Destabilizing	0.85	D	0.801	deleterious	None	None	None	None	N
C/F	0.5168	ambiguous	0.5966	pathogenic	-1.198	Destabilizing	0.009	N	0.678	prob.neutral	N	0.510597532	None	None	N
C/G	0.5038	ambiguous	0.5944	pathogenic	-2.028	Highly Destabilizing	0.549	D	0.767	deleterious	N	0.453013453	None	None	N
C/H	0.9446	likely_pathogenic	0.9678	pathogenic	-2.383	Highly Destabilizing	0.992	D	0.79	deleterious	None	None	None	None	N
C/I	0.7144	likely_pathogenic	0.7723	pathogenic	-0.765	Destabilizing	0.447	N	0.785	deleterious	None	None	None	None	N
C/K	0.9951	likely_pathogenic	0.9972	pathogenic	-1.188	Destabilizing	0.85	D	0.804	deleterious	None	None	None	None	N
C/L	0.6467	likely_pathogenic	0.6916	pathogenic	-0.765	Destabilizing	0.447	N	0.747	deleterious	None	None	None	None	N
C/M	0.8304	likely_pathogenic	0.8643	pathogenic	0.164	Stabilizing	0.92	D	0.773	deleterious	None	None	None	None	N
C/N	0.9594	likely_pathogenic	0.9791	pathogenic	-1.713	Destabilizing	0.85	D	0.799	deleterious	None	None	None	None	N
C/P	0.9947	likely_pathogenic	0.9966	pathogenic	-1.048	Destabilizing	0.92	D	0.813	deleterious	None	None	None	None	N
C/Q	0.9795	likely_pathogenic	0.9877	pathogenic	-1.323	Destabilizing	0.92	D	0.802	deleterious	None	None	None	None	N
C/R	0.9551	likely_pathogenic	0.9712	pathogenic	-1.535	Destabilizing	0.896	D	0.815	deleterious	N	0.494051999	None	None	N
C/S	0.6146	likely_pathogenic	0.7231	pathogenic	-2.0	Highly Destabilizing	0.045	N	0.621	neutral	N	0.422015755	None	None	N
C/T	0.7831	likely_pathogenic	0.8401	pathogenic	-1.608	Destabilizing	0.447	N	0.761	deleterious	None	None	None	None	N
C/V	0.5535	ambiguous	0.6012	pathogenic	-1.048	Destabilizing	0.447	N	0.755	deleterious	None	None	None	None	N
C/W	0.8986	likely_pathogenic	0.9379	pathogenic	-1.591	Destabilizing	0.99	D	0.777	deleterious	N	0.504981069	None	None	N
C/Y	0.7753	likely_pathogenic	0.8529	pathogenic	-1.377	Destabilizing	0.681	D	0.793	deleterious	N	0.4896649	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.