TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15204	45835;45836;45837	chr2:178621108;178621107;178621106	chr2:179485835;179485834;179485833
N2AB	13563	40912;40913;40914	chr2:178621108;178621107;178621106	chr2:179485835;179485834;179485833
N2A	12636	38131;38132;38133	chr2:178621108;178621107;178621106	chr2:179485835;179485834;179485833
N2B	6139	18640;18641;18642	chr2:178621108;178621107;178621106	chr2:179485835;179485834;179485833
Novex-1	6264	19015;19016;19017	chr2:178621108;178621107;178621106	chr2:179485835;179485834;179485833
Novex-2	6331	19216;19217;19218	chr2:178621108;178621107;178621106	chr2:179485835;179485834;179485833
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-103
• Domain position: 85
• Structural Position: 178
• Q(SASA): 0.2576
• 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
V/D	rs1337863742	-2.346	0.998	D	0.711	0.826	0.876902895405	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.96E-06	0
V/D	rs1337863742	-2.346	0.998	D	0.711	0.826	0.876902895405	gnomAD-4.0.0	1.59547E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86261E-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
V/A	0.8996	likely_pathogenic	0.8834	pathogenic	-2.185	Highly Destabilizing	0.973	D	0.491	neutral	D	0.76816884	None	None	N
V/C	0.9878	likely_pathogenic	0.98	pathogenic	-1.804	Destabilizing	1.0	D	0.596	neutral	None	None	None	None	N
V/D	0.9968	likely_pathogenic	0.9976	pathogenic	-2.798	Highly Destabilizing	0.998	D	0.711	prob.delet.	D	0.770357693	None	None	N
V/E	0.9905	likely_pathogenic	0.9933	pathogenic	-2.669	Highly Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
V/F	0.9173	likely_pathogenic	0.9156	pathogenic	-1.37	Destabilizing	0.999	D	0.585	neutral	D	0.76967584	None	None	N
V/G	0.944	likely_pathogenic	0.949	pathogenic	-2.616	Highly Destabilizing	0.217	N	0.46	neutral	D	0.770357693	None	None	N
V/H	0.998	likely_pathogenic	0.9982	pathogenic	-2.116	Highly Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
V/I	0.1241	likely_benign	0.1165	benign	-1.014	Destabilizing	0.998	D	0.501	neutral	D	0.59371682	None	None	N
V/K	0.992	likely_pathogenic	0.9939	pathogenic	-1.786	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
V/L	0.6904	likely_pathogenic	0.6698	pathogenic	-1.014	Destabilizing	0.996	D	0.509	neutral	D	0.730589096	None	None	N
V/M	0.7633	likely_pathogenic	0.7644	pathogenic	-1.066	Destabilizing	1.0	D	0.593	neutral	None	None	None	None	N
V/N	0.9877	likely_pathogenic	0.9879	pathogenic	-1.929	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
V/P	0.9875	likely_pathogenic	0.9832	pathogenic	-1.378	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
V/Q	0.9921	likely_pathogenic	0.9936	pathogenic	-1.948	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
V/R	0.9881	likely_pathogenic	0.9906	pathogenic	-1.387	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
V/S	0.972	likely_pathogenic	0.9708	pathogenic	-2.492	Highly Destabilizing	0.998	D	0.674	neutral	None	None	None	None	N
V/T	0.919	likely_pathogenic	0.9157	pathogenic	-2.249	Highly Destabilizing	0.996	D	0.563	neutral	None	None	None	None	N
V/W	0.9992	likely_pathogenic	0.9991	pathogenic	-1.743	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
V/Y	0.9956	likely_pathogenic	0.9953	pathogenic	-1.461	Destabilizing	1.0	D	0.585	neutral	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.