TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6265	19018;19019;19020	chr2:178729363;178729362;178729361	chr2:179594090;179594089;179594088
N2AB	5948	18067;18068;18069	chr2:178729363;178729362;178729361	chr2:179594090;179594089;179594088
N2A	5021	15286;15287;15288	chr2:178729363;178729362;178729361	chr2:179594090;179594089;179594088
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: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-46
• Domain position: 67
• Structural Position: 149
• Q(SASA): 0.1442
• 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
D/G	rs1403981596	-1.004	0.928	D	0.771	0.849	0.718210980111	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
D/G	rs1403981596	-1.004	0.928	D	0.771	0.849	0.718210980111	gnomAD-4.0.0	1.59169E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85915E-06	0	0
D/H	rs764050491	-0.48	0.997	D	0.819	0.732	0.711559257315	gnomAD-4.0.0	1.5917E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88288E-05	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
D/A	0.8817	likely_pathogenic	0.8529	pathogenic	0.529	Stabilizing	0.957	D	0.826	deleterious	D	0.632032093	None	None	N
D/C	0.9645	likely_pathogenic	0.9525	pathogenic	0.453	Stabilizing	0.999	D	0.824	deleterious	None	None	None	None	N
D/E	0.646	likely_pathogenic	0.6216	pathogenic	-0.609	Destabilizing	0.039	N	0.353	neutral	D	0.618748705	None	None	N
D/F	0.9816	likely_pathogenic	0.9777	pathogenic	0.992	Stabilizing	0.999	D	0.877	deleterious	None	None	None	None	N
D/G	0.926	likely_pathogenic	0.9021	pathogenic	0.041	Stabilizing	0.928	D	0.771	deleterious	D	0.657539844	None	None	N
D/H	0.9081	likely_pathogenic	0.8885	pathogenic	0.533	Stabilizing	0.997	D	0.819	deleterious	D	0.586002771	None	None	N
D/I	0.9578	likely_pathogenic	0.9506	pathogenic	1.846	Stabilizing	0.992	D	0.871	deleterious	None	None	None	None	N
D/K	0.9711	likely_pathogenic	0.9642	pathogenic	0.266	Stabilizing	0.968	D	0.805	deleterious	None	None	None	None	N
D/L	0.9573	likely_pathogenic	0.9544	pathogenic	1.846	Stabilizing	0.983	D	0.877	deleterious	None	None	None	None	N
D/M	0.9738	likely_pathogenic	0.9719	pathogenic	2.332	Highly Stabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
D/N	0.668	likely_pathogenic	0.6073	pathogenic	-0.593	Destabilizing	0.978	D	0.783	deleterious	D	0.604879547	None	None	N
D/P	0.995	likely_pathogenic	0.9942	pathogenic	1.437	Stabilizing	0.992	D	0.821	deleterious	None	None	None	None	N
D/Q	0.9292	likely_pathogenic	0.9138	pathogenic	-0.16	Destabilizing	0.968	D	0.795	deleterious	None	None	None	None	N
D/R	0.974	likely_pathogenic	0.9702	pathogenic	0.074	Stabilizing	0.983	D	0.867	deleterious	None	None	None	None	N
D/S	0.7993	likely_pathogenic	0.7487	pathogenic	-0.897	Destabilizing	0.895	D	0.693	prob.neutral	None	None	None	None	N
D/T	0.9348	likely_pathogenic	0.9187	pathogenic	-0.431	Destabilizing	0.983	D	0.819	deleterious	None	None	None	None	N
D/V	0.8972	likely_pathogenic	0.8813	pathogenic	1.437	Stabilizing	0.978	D	0.877	deleterious	D	0.657943452	None	None	N
D/W	0.9971	likely_pathogenic	0.9967	pathogenic	0.887	Stabilizing	0.999	D	0.8	deleterious	None	None	None	None	N
D/Y	0.9128	likely_pathogenic	0.8957	pathogenic	1.226	Stabilizing	0.999	D	0.877	deleterious	D	0.641722287	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.