TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6690	20293;20294;20295	chr2:178727297;178727296;178727295	chr2:179592024;179592023;179592022
N2AB	6373	19342;19343;19344	chr2:178727297;178727296;178727295	chr2:179592024;179592023;179592022
N2A	5446	16561;16562;16563	chr2:178727297;178727296;178727295	chr2:179592024;179592023;179592022
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-51
• Domain position: 24
• Structural Position: 34
• Q(SASA): 0.3851
• 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
K/E	None	None	0.993	D	0.502	0.318	0.430694319191	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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
K/A	0.6103	likely_pathogenic	0.7409	pathogenic	-0.807	Destabilizing	0.995	D	0.573	neutral	None	None	None	None	N
K/C	0.8543	likely_pathogenic	0.9028	pathogenic	-0.859	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
K/D	0.8594	likely_pathogenic	0.9087	pathogenic	-0.221	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
K/E	0.2709	likely_benign	0.4125	ambiguous	-0.061	Destabilizing	0.993	D	0.502	neutral	D	0.524842706	None	None	N
K/F	0.8994	likely_pathogenic	0.9401	pathogenic	-0.295	Destabilizing	0.993	D	0.755	deleterious	None	None	None	None	N
K/G	0.8012	likely_pathogenic	0.8657	pathogenic	-1.217	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
K/H	0.4045	ambiguous	0.4964	ambiguous	-1.393	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
K/I	0.4962	ambiguous	0.6226	pathogenic	0.282	Stabilizing	0.843	D	0.717	prob.delet.	None	None	None	None	N
K/L	0.5522	ambiguous	0.669	pathogenic	0.282	Stabilizing	0.01	N	0.54	neutral	None	None	None	None	N
K/M	0.3452	ambiguous	0.4701	ambiguous	0.074	Stabilizing	0.971	D	0.749	deleterious	N	0.499623664	None	None	N
K/N	0.7092	likely_pathogenic	0.804	pathogenic	-0.775	Destabilizing	0.999	D	0.68	prob.neutral	N	0.492493639	None	None	N
K/P	0.9654	likely_pathogenic	0.9737	pathogenic	-0.052	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
K/Q	0.1521	likely_benign	0.2069	benign	-0.753	Destabilizing	0.995	D	0.671	neutral	N	0.517916733	None	None	N
K/R	0.0927	likely_benign	0.0971	benign	-0.717	Destabilizing	0.989	D	0.494	neutral	N	0.513414991	None	None	N
K/S	0.6687	likely_pathogenic	0.7764	pathogenic	-1.495	Destabilizing	0.998	D	0.557	neutral	None	None	None	None	N
K/T	0.2982	likely_benign	0.4166	ambiguous	-1.108	Destabilizing	0.994	D	0.722	prob.delet.	D	0.523975914	None	None	N
K/V	0.4499	ambiguous	0.5699	pathogenic	-0.052	Destabilizing	0.669	D	0.655	neutral	None	None	None	None	N
K/W	0.8865	likely_pathogenic	0.9241	pathogenic	-0.153	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
K/Y	0.7935	likely_pathogenic	0.8606	pathogenic	0.13	Stabilizing	0.991	D	0.744	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.