TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31303	94132;94133;94134	chr2:178547719;178547718;178547717	chr2:179412446;179412445;179412444
N2AB	29662	89209;89210;89211	chr2:178547719;178547718;178547717	chr2:179412446;179412445;179412444
N2A	28735	86428;86429;86430	chr2:178547719;178547718;178547717	chr2:179412446;179412445;179412444
N2B	22238	66937;66938;66939	chr2:178547719;178547718;178547717	chr2:179412446;179412445;179412444
Novex-1	22363	67312;67313;67314	chr2:178547719;178547718;178547717	chr2:179412446;179412445;179412444
Novex-2	22430	67513;67514;67515	chr2:178547719;178547718;178547717	chr2:179412446;179412445;179412444
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-151
• Domain position: 86
• Structural Position: 174
• Q(SASA): 0.1507
• 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/A	rs1697801738	None	0.999	N	0.613	0.481	0.648577244254	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	2.75482E-04	None	0	0	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
V/A	0.7	likely_pathogenic	0.6147	pathogenic	-2.017	Highly Destabilizing	0.999	D	0.613	neutral	N	0.501885166	None	None	N
V/C	0.9613	likely_pathogenic	0.9438	pathogenic	-1.602	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
V/D	0.9984	likely_pathogenic	0.9978	pathogenic	-2.722	Highly Destabilizing	1.0	D	0.865	deleterious	N	0.502392145	None	None	N
V/E	0.9953	likely_pathogenic	0.9936	pathogenic	-2.429	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
V/F	0.888	likely_pathogenic	0.8784	pathogenic	-1.142	Destabilizing	1.0	D	0.831	deleterious	N	0.501124698	None	None	N
V/G	0.9239	likely_pathogenic	0.8919	pathogenic	-2.625	Highly Destabilizing	1.0	D	0.861	deleterious	N	0.502392145	None	None	N
V/H	0.9984	likely_pathogenic	0.9976	pathogenic	-2.557	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
V/I	0.1166	likely_benign	0.1143	benign	-0.283	Destabilizing	0.997	D	0.536	neutral	N	0.449381289	None	None	N
V/K	0.9955	likely_pathogenic	0.9943	pathogenic	-1.583	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
V/L	0.7147	likely_pathogenic	0.6659	pathogenic	-0.283	Destabilizing	0.997	D	0.635	neutral	N	0.478068534	None	None	N
V/M	0.6716	likely_pathogenic	0.6273	pathogenic	-0.521	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
V/N	0.9931	likely_pathogenic	0.9892	pathogenic	-2.135	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/P	0.9935	likely_pathogenic	0.9895	pathogenic	-0.837	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
V/Q	0.9943	likely_pathogenic	0.9922	pathogenic	-1.818	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
V/R	0.9918	likely_pathogenic	0.9892	pathogenic	-1.683	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/S	0.9592	likely_pathogenic	0.9311	pathogenic	-2.742	Highly Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
V/T	0.8458	likely_pathogenic	0.7827	pathogenic	-2.284	Highly Destabilizing	0.999	D	0.652	neutral	None	None	None	None	N
V/W	0.9989	likely_pathogenic	0.9987	pathogenic	-1.723	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
V/Y	0.9937	likely_pathogenic	0.9919	pathogenic	-1.309	Destabilizing	1.0	D	0.827	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.