TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22172	66739;66740;66741	chr2:178581754;178581753;178581752	chr2:179446481;179446480;179446479
N2AB	20531	61816;61817;61818	chr2:178581754;178581753;178581752	chr2:179446481;179446480;179446479
N2A	19604	59035;59036;59037	chr2:178581754;178581753;178581752	chr2:179446481;179446480;179446479
N2B	13107	39544;39545;39546	chr2:178581754;178581753;178581752	chr2:179446481;179446480;179446479
Novex-1	13232	39919;39920;39921	chr2:178581754;178581753;178581752	chr2:179446481;179446480;179446479
Novex-2	13299	40120;40121;40122	chr2:178581754;178581753;178581752	chr2:179446481;179446480;179446479
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-49
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.1636
• 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
S/Y	rs1455920569	-0.731	0.999	N	0.777	0.417	0.749682748319	gnomAD-2.1.1	4.22E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.7301E-04
S/Y	rs1455920569	-0.731	0.999	N	0.777	0.417	0.749682748319	gnomAD-4.0.0	1.60848E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.42601E-04	0	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
S/A	0.2899	likely_benign	0.2656	benign	-0.358	Destabilizing	0.973	D	0.394	neutral	N	0.483381243	None	None	N
S/C	0.2842	likely_benign	0.2769	benign	-0.97	Destabilizing	1.0	D	0.713	prob.delet.	N	0.495119623	None	None	N
S/D	0.9211	likely_pathogenic	0.92	pathogenic	-1.921	Destabilizing	0.996	D	0.497	neutral	None	None	None	None	N
S/E	0.9456	likely_pathogenic	0.9415	pathogenic	-1.882	Destabilizing	0.996	D	0.501	neutral	None	None	None	None	N
S/F	0.7394	likely_pathogenic	0.7016	pathogenic	-0.984	Destabilizing	0.999	D	0.785	deleterious	N	0.503259925	None	None	N
S/G	0.3091	likely_benign	0.3067	benign	-0.534	Destabilizing	0.996	D	0.413	neutral	None	None	None	None	N
S/H	0.6529	likely_pathogenic	0.6527	pathogenic	-1.098	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
S/I	0.8413	likely_pathogenic	0.7955	pathogenic	0.005	Stabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
S/K	0.9327	likely_pathogenic	0.9293	pathogenic	-0.435	Destabilizing	0.996	D	0.493	neutral	None	None	None	None	N
S/L	0.4992	ambiguous	0.4522	ambiguous	0.005	Stabilizing	0.992	D	0.635	neutral	None	None	None	None	N
S/M	0.5561	ambiguous	0.5276	ambiguous	0.109	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
S/N	0.5912	likely_pathogenic	0.5765	pathogenic	-0.927	Destabilizing	0.996	D	0.511	neutral	None	None	None	None	N
S/P	0.9959	likely_pathogenic	0.9961	pathogenic	-0.087	Destabilizing	0.999	D	0.731	prob.delet.	D	0.544076791	None	None	N
S/Q	0.8674	likely_pathogenic	0.8656	pathogenic	-1.185	Destabilizing	1.0	D	0.631	neutral	None	None	None	None	N
S/R	0.913	likely_pathogenic	0.9076	pathogenic	-0.297	Destabilizing	0.999	D	0.746	deleterious	None	None	None	None	N
S/T	0.0902	likely_benign	0.0893	benign	-0.625	Destabilizing	0.543	D	0.369	neutral	N	0.461959089	None	None	N
S/V	0.7227	likely_pathogenic	0.678	pathogenic	-0.087	Destabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	N
S/W	0.8472	likely_pathogenic	0.8335	pathogenic	-1.164	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
S/Y	0.6627	likely_pathogenic	0.638	pathogenic	-0.685	Destabilizing	0.999	D	0.777	deleterious	N	0.486116721	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.