TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7285	22078;22079;22080	chr2:178723154;178723153;178723152	chr2:179587881;179587880;179587879
N2AB	6968	21127;21128;21129	chr2:178723154;178723153;178723152	chr2:179587881;179587880;179587879
N2A	6041	18346;18347;18348	chr2:178723154;178723153;178723152	chr2:179587881;179587880;179587879
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-57
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.1253
• 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	rs2154302642	None	0.938	N	0.779	0.36	0.565902896228	gnomAD-4.0.0	3.18396E-06	None	None	None	None	N	None	0	0	None	0	2.77454E-05	None	0	0	0	1.43303E-05	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	0.2476	likely_benign	0.2442	benign	-1.633	Destabilizing	0.905	D	0.656	neutral	None	None	None	None	N
C/D	0.9394	likely_pathogenic	0.9429	pathogenic	-1.481	Destabilizing	0.996	D	0.814	deleterious	None	None	None	None	N
C/E	0.9708	likely_pathogenic	0.9726	pathogenic	-1.257	Destabilizing	0.996	D	0.802	deleterious	None	None	None	None	N
C/F	0.5083	ambiguous	0.4878	ambiguous	-1.126	Destabilizing	0.938	D	0.78	deleterious	N	0.456587032	None	None	N
C/G	0.1197	likely_benign	0.1517	benign	-1.979	Destabilizing	0.984	D	0.786	deleterious	N	0.499343176	None	None	N
C/H	0.8423	likely_pathogenic	0.8358	pathogenic	-2.298	Highly Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
C/I	0.66	likely_pathogenic	0.6403	pathogenic	-0.704	Destabilizing	0.988	D	0.751	deleterious	None	None	None	None	N
C/K	0.9784	likely_pathogenic	0.9775	pathogenic	-1.047	Destabilizing	0.996	D	0.813	deleterious	None	None	None	None	N
C/L	0.6125	likely_pathogenic	0.5917	pathogenic	-0.704	Destabilizing	0.919	D	0.723	prob.delet.	None	None	None	None	N
C/M	0.7697	likely_pathogenic	0.7536	pathogenic	0.053	Stabilizing	0.999	D	0.746	deleterious	None	None	None	None	N
C/N	0.7709	likely_pathogenic	0.7765	pathogenic	-1.599	Destabilizing	0.996	D	0.814	deleterious	None	None	None	None	N
C/P	0.9898	likely_pathogenic	0.9887	pathogenic	-0.991	Destabilizing	0.996	D	0.814	deleterious	None	None	None	None	N
C/Q	0.9082	likely_pathogenic	0.9066	pathogenic	-1.16	Destabilizing	0.996	D	0.809	deleterious	None	None	None	None	N
C/R	0.867	likely_pathogenic	0.8682	pathogenic	-1.474	Destabilizing	0.995	D	0.815	deleterious	N	0.487856745	None	None	N
C/S	0.2204	likely_benign	0.2375	benign	-1.89	Destabilizing	0.984	D	0.761	deleterious	N	0.431982033	None	None	N
C/T	0.3724	ambiguous	0.3793	ambiguous	-1.483	Destabilizing	0.988	D	0.758	deleterious	None	None	None	None	N
C/V	0.4707	ambiguous	0.4587	ambiguous	-0.991	Destabilizing	0.959	D	0.74	deleterious	None	None	None	None	N
C/W	0.8744	likely_pathogenic	0.8661	pathogenic	-1.531	Destabilizing	0.059	N	0.644	neutral	N	0.465198314	None	None	N
C/Y	0.6785	likely_pathogenic	0.6724	pathogenic	-1.304	Destabilizing	0.938	D	0.779	deleterious	N	0.50825066	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.