TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29709	89350;89351;89352	chr2:178553986;178553985;178553984	chr2:179418713;179418712;179418711
N2AB	28068	84427;84428;84429	chr2:178553986;178553985;178553984	chr2:179418713;179418712;179418711
N2A	27141	81646;81647;81648	chr2:178553986;178553985;178553984	chr2:179418713;179418712;179418711
N2B	20644	62155;62156;62157	chr2:178553986;178553985;178553984	chr2:179418713;179418712;179418711
Novex-1	20769	62530;62531;62532	chr2:178553986;178553985;178553984	chr2:179418713;179418712;179418711
Novex-2	20836	62731;62732;62733	chr2:178553986;178553985;178553984	chr2:179418713;179418712;179418711
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: Fn3-104
• Domain position: 77
• Structural Position: 109
• Q(SASA): 0.0573
• 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	0.963	N	0.743	0.306	0.715593384032	gnomAD-4.0.0	1.59369E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85858E-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	0.2977	likely_benign	0.2845	benign	-1.412	Destabilizing	0.25	N	0.591	neutral	None	None	None	None	N
C/D	0.9527	likely_pathogenic	0.9553	pathogenic	-1.608	Destabilizing	0.85	D	0.758	deleterious	None	None	None	None	N
C/E	0.9525	likely_pathogenic	0.9492	pathogenic	-1.363	Destabilizing	0.85	D	0.755	deleterious	None	None	None	None	N
C/F	0.3977	ambiguous	0.3761	ambiguous	-0.848	Destabilizing	0.81	D	0.746	deleterious	N	0.423203126	None	None	N
C/G	0.2528	likely_benign	0.253	benign	-1.715	Destabilizing	0.379	N	0.735	prob.delet.	N	0.50866724	None	None	N
C/H	0.7278	likely_pathogenic	0.7133	pathogenic	-1.839	Destabilizing	0.977	D	0.741	deleterious	None	None	None	None	N
C/I	0.7119	likely_pathogenic	0.7161	pathogenic	-0.581	Destabilizing	0.447	N	0.753	deleterious	None	None	None	None	N
C/K	0.92	likely_pathogenic	0.906	pathogenic	-0.993	Destabilizing	0.739	D	0.741	deleterious	None	None	None	None	N
C/L	0.6121	likely_pathogenic	0.5924	pathogenic	-0.581	Destabilizing	0.005	N	0.509	neutral	None	None	None	None	N
C/M	0.655	likely_pathogenic	0.6617	pathogenic	-0.99	Destabilizing	0.85	D	0.758	deleterious	None	None	None	None	N
C/N	0.7221	likely_pathogenic	0.7319	pathogenic	-1.571	Destabilizing	0.739	D	0.761	deleterious	None	None	None	None	N
C/P	0.9976	likely_pathogenic	0.9976	pathogenic	-0.841	Destabilizing	0.92	D	0.767	deleterious	None	None	None	None	N
C/Q	0.7606	likely_pathogenic	0.7564	pathogenic	-1.069	Destabilizing	0.85	D	0.767	deleterious	None	None	None	None	N
C/R	0.6855	likely_pathogenic	0.6589	pathogenic	-1.499	Destabilizing	0.81	D	0.766	deleterious	N	0.404865295	None	None	N
C/S	0.2377	likely_benign	0.2438	benign	-1.793	Destabilizing	0.007	N	0.461	neutral	N	0.375179893	None	None	N
C/T	0.5116	ambiguous	0.5269	ambiguous	-1.398	Destabilizing	0.447	N	0.741	deleterious	None	None	None	None	N
C/V	0.5692	likely_pathogenic	0.5672	pathogenic	-0.841	Destabilizing	0.447	N	0.738	prob.delet.	None	None	None	None	N
C/W	0.7931	likely_pathogenic	0.7798	pathogenic	-1.298	Destabilizing	0.99	D	0.714	prob.delet.	N	0.47357083	None	None	N
C/Y	0.5478	ambiguous	0.4969	ambiguous	-1.039	Destabilizing	0.963	D	0.743	deleterious	N	0.39961419	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.