TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20420	61483;61484;61485	chr2:178590467;178590466;178590465	chr2:179455194;179455193;179455192
N2AB	18779	56560;56561;56562	chr2:178590467;178590466;178590465	chr2:179455194;179455193;179455192
N2A	17852	53779;53780;53781	chr2:178590467;178590466;178590465	chr2:179455194;179455193;179455192
N2B	11355	34288;34289;34290	chr2:178590467;178590466;178590465	chr2:179455194;179455193;179455192
Novex-1	11480	34663;34664;34665	chr2:178590467;178590466;178590465	chr2:179455194;179455193;179455192
Novex-2	11547	34864;34865;34866	chr2:178590467;178590466;178590465	chr2:179455194;179455193;179455192
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Fn3-36
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.5163
• 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
R/S	rs750271660	None	0.92	N	0.499	0.252	0.259761712551	gnomAD-4.0.0	3.90161E-05	None	None	None	None	N	None	2.99061E-05	0	None	0	0	None	0	0	5.03848E-05	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
R/A	0.6899	likely_pathogenic	0.5632	ambiguous	-0.96	Destabilizing	0.863	D	0.502	neutral	None	None	None	None	N
R/C	0.2717	likely_benign	0.246	benign	-0.904	Destabilizing	0.999	D	0.649	neutral	None	None	None	None	N
R/D	0.9164	likely_pathogenic	0.8704	pathogenic	-0.197	Destabilizing	0.969	D	0.601	neutral	None	None	None	None	N
R/E	0.6902	likely_pathogenic	0.5829	pathogenic	-0.077	Destabilizing	0.863	D	0.481	neutral	None	None	None	None	N
R/F	0.8539	likely_pathogenic	0.7985	pathogenic	-0.777	Destabilizing	0.997	D	0.645	neutral	None	None	None	None	N
R/G	0.6769	likely_pathogenic	0.5688	pathogenic	-1.273	Destabilizing	0.959	D	0.555	neutral	N	0.473686189	None	None	N
R/H	0.2211	likely_benign	0.1968	benign	-1.472	Destabilizing	0.997	D	0.548	neutral	None	None	None	None	N
R/I	0.4545	ambiguous	0.3462	ambiguous	-0.116	Destabilizing	0.997	D	0.647	neutral	None	None	None	None	N
R/K	0.1541	likely_benign	0.1351	benign	-1.064	Destabilizing	0.021	N	0.166	neutral	N	0.401713133	None	None	N
R/L	0.4724	ambiguous	0.3914	ambiguous	-0.116	Destabilizing	0.969	D	0.555	neutral	None	None	None	None	N
R/M	0.5559	ambiguous	0.4659	ambiguous	-0.381	Destabilizing	0.996	D	0.604	neutral	N	0.518942949	None	None	N
R/N	0.8386	likely_pathogenic	0.7841	pathogenic	-0.458	Destabilizing	0.969	D	0.485	neutral	None	None	None	None	N
R/P	0.6828	likely_pathogenic	0.5556	ambiguous	-0.378	Destabilizing	0.997	D	0.623	neutral	None	None	None	None	N
R/Q	0.18	likely_benign	0.1546	benign	-0.651	Destabilizing	0.939	D	0.499	neutral	None	None	None	None	N
R/S	0.8066	likely_pathogenic	0.7268	pathogenic	-1.261	Destabilizing	0.92	D	0.499	neutral	N	0.489830763	None	None	N
R/T	0.4923	ambiguous	0.3523	ambiguous	-0.962	Destabilizing	0.959	D	0.533	neutral	N	0.457334342	None	None	N
R/V	0.5206	ambiguous	0.413	ambiguous	-0.378	Destabilizing	0.991	D	0.606	neutral	None	None	None	None	N
R/W	0.4305	ambiguous	0.3712	ambiguous	-0.386	Destabilizing	0.999	D	0.675	prob.neutral	N	0.484789005	None	None	N
R/Y	0.7033	likely_pathogenic	0.6385	pathogenic	-0.113	Destabilizing	0.997	D	0.649	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.