TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18777	56554;56555;56556	chr2:178599572;178599571;178599570	chr2:179464299;179464298;179464297
N2AB	17136	51631;51632;51633	chr2:178599572;178599571;178599570	chr2:179464299;179464298;179464297
N2A	16209	48850;48851;48852	chr2:178599572;178599571;178599570	chr2:179464299;179464298;179464297
N2B	9712	29359;29360;29361	chr2:178599572;178599571;178599570	chr2:179464299;179464298;179464297
Novex-1	9837	29734;29735;29736	chr2:178599572;178599571;178599570	chr2:179464299;179464298;179464297
Novex-2	9904	29935;29936;29937	chr2:178599572;178599571;178599570	chr2:179464299;179464298;179464297
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-116
• Domain position: 90
• Structural Position: 172
• Q(SASA): 0.081
• 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
M/L	rs1369067866	-0.714	0.166	N	0.187	0.179	0.314716216878	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14732E-04	0	None	0	0	None	0	None	0	0	0
M/L	rs1369067866	-0.714	0.166	N	0.187	0.179	0.314716216878	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
M/L	rs1369067866	-0.714	0.166	N	0.187	0.179	0.314716216878	gnomAD-4.0.0	6.57626E-06	None	None	None	None	N	None	2.41418E-05	0	None	0	0	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
M/A	0.8478	likely_pathogenic	0.7817	pathogenic	-2.341	Highly Destabilizing	0.55	D	0.558	neutral	None	None	None	None	N
M/C	0.8584	likely_pathogenic	0.8103	pathogenic	-2.613	Highly Destabilizing	0.993	D	0.713	prob.delet.	None	None	None	None	N
M/D	0.9973	likely_pathogenic	0.9954	pathogenic	-2.26	Highly Destabilizing	0.932	D	0.769	deleterious	None	None	None	None	N
M/E	0.9773	likely_pathogenic	0.961	pathogenic	-2.005	Highly Destabilizing	0.932	D	0.7	prob.neutral	None	None	None	None	N
M/F	0.6608	likely_pathogenic	0.6354	pathogenic	-0.748	Destabilizing	0.932	D	0.602	neutral	None	None	None	None	N
M/G	0.9624	likely_pathogenic	0.9299	pathogenic	-2.848	Highly Destabilizing	0.932	D	0.711	prob.delet.	None	None	None	None	N
M/H	0.9797	likely_pathogenic	0.9655	pathogenic	-2.493	Highly Destabilizing	0.993	D	0.711	prob.delet.	None	None	None	None	N
M/I	0.5076	ambiguous	0.4505	ambiguous	-0.874	Destabilizing	0.01	N	0.117	neutral	N	0.379386139	None	None	N
M/K	0.919	likely_pathogenic	0.8709	pathogenic	-1.707	Destabilizing	0.912	D	0.664	neutral	N	0.485123352	None	None	N
M/L	0.2773	likely_benign	0.2421	benign	-0.874	Destabilizing	0.166	N	0.187	neutral	N	0.457825493	None	None	N
M/N	0.9679	likely_pathogenic	0.9499	pathogenic	-2.143	Highly Destabilizing	0.932	D	0.749	deleterious	None	None	None	None	N
M/P	0.9973	likely_pathogenic	0.9949	pathogenic	-1.347	Destabilizing	0.977	D	0.764	deleterious	None	None	None	None	N
M/Q	0.889	likely_pathogenic	0.8248	pathogenic	-1.783	Destabilizing	0.993	D	0.667	neutral	None	None	None	None	N
M/R	0.9373	likely_pathogenic	0.8902	pathogenic	-1.795	Destabilizing	0.912	D	0.739	prob.delet.	N	0.503832715	None	None	N
M/S	0.9403	likely_pathogenic	0.9031	pathogenic	-2.702	Highly Destabilizing	0.584	D	0.635	neutral	None	None	None	None	N
M/T	0.8243	likely_pathogenic	0.7402	pathogenic	-2.315	Highly Destabilizing	0.028	N	0.347	neutral	N	0.443533618	None	None	N
M/V	0.2094	likely_benign	0.1775	benign	-1.347	Destabilizing	0.166	N	0.343	neutral	N	0.415613511	None	None	N
M/W	0.9678	likely_pathogenic	0.9493	pathogenic	-1.12	Destabilizing	0.998	D	0.687	prob.neutral	None	None	None	None	N
M/Y	0.934	likely_pathogenic	0.9073	pathogenic	-1.11	Destabilizing	0.993	D	0.748	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.