TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3085	9478;9479;9480	chr2:178768066;178768065;178768064	chr2:179632793;179632792;179632791
N2AB	3085	9478;9479;9480	chr2:178768066;178768065;178768064	chr2:179632793;179632792;179632791
N2A	3085	9478;9479;9480	chr2:178768066;178768065;178768064	chr2:179632793;179632792;179632791
N2B	3039	9340;9341;9342	chr2:178768066;178768065;178768064	chr2:179632793;179632792;179632791
Novex-1	3039	9340;9341;9342	chr2:178768066;178768065;178768064	chr2:179632793;179632792;179632791
Novex-2	3039	9340;9341;9342	chr2:178768066;178768065;178768064	chr2:179632793;179632792;179632791
Novex-3	3085	9478;9479;9480	chr2:178768066;178768065;178768064	chr2:179632793;179632792;179632791

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-21
• Domain position: 28
• Structural Position: 43
• Q(SASA): 1.0057
• 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	None	None	0.334	N	0.441	0.406	0.28492961333	gnomAD-4.0.0	1.20034E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31252E-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
D/A	0.4973	ambiguous	0.4412	ambiguous	-0.493	Destabilizing	0.549	D	0.501	neutral	N	0.506863568	None	None	N
D/C	0.9331	likely_pathogenic	0.9253	pathogenic	-0.308	Destabilizing	0.992	D	0.564	neutral	None	None	None	None	N
D/E	0.3319	likely_benign	0.2924	benign	-0.548	Destabilizing	0.334	N	0.423	neutral	N	0.498204138	None	None	N
D/F	0.8842	likely_pathogenic	0.8689	pathogenic	-0.044	Destabilizing	0.85	D	0.522	neutral	None	None	None	None	N
D/G	0.3756	ambiguous	0.318	benign	-0.803	Destabilizing	0.334	N	0.441	neutral	N	0.500512962	None	None	N
D/H	0.7164	likely_pathogenic	0.6593	pathogenic	-0.127	Destabilizing	0.009	N	0.342	neutral	D	0.57697762	None	None	N
D/I	0.8676	likely_pathogenic	0.8442	pathogenic	0.313	Stabilizing	0.92	D	0.527	neutral	None	None	None	None	N
D/K	0.8666	likely_pathogenic	0.8287	pathogenic	-0.391	Destabilizing	0.617	D	0.472	neutral	None	None	None	None	N
D/L	0.7735	likely_pathogenic	0.7628	pathogenic	0.313	Stabilizing	0.85	D	0.509	neutral	None	None	None	None	N
D/M	0.8995	likely_pathogenic	0.8905	pathogenic	0.543	Stabilizing	0.992	D	0.523	neutral	None	None	None	None	N
D/N	0.1772	likely_benign	0.161	benign	-0.777	Destabilizing	0.007	N	0.201	neutral	N	0.474042299	None	None	N
D/P	0.9712	likely_pathogenic	0.9636	pathogenic	0.068	Stabilizing	0.972	D	0.474	neutral	None	None	None	None	N
D/Q	0.7764	likely_pathogenic	0.715	pathogenic	-0.652	Destabilizing	0.85	D	0.415	neutral	None	None	None	None	N
D/R	0.8737	likely_pathogenic	0.8333	pathogenic	-0.071	Destabilizing	0.85	D	0.493	neutral	None	None	None	None	N
D/S	0.3217	likely_benign	0.2773	benign	-0.976	Destabilizing	0.617	D	0.413	neutral	None	None	None	None	N
D/T	0.6417	likely_pathogenic	0.6019	pathogenic	-0.73	Destabilizing	0.617	D	0.472	neutral	None	None	None	None	N
D/V	0.7029	likely_pathogenic	0.6625	pathogenic	0.068	Stabilizing	0.896	D	0.523	neutral	N	0.511356122	None	None	N
D/W	0.9841	likely_pathogenic	0.9799	pathogenic	0.152	Stabilizing	0.992	D	0.615	neutral	None	None	None	None	N
D/Y	0.6119	likely_pathogenic	0.5732	pathogenic	0.181	Stabilizing	0.681	D	0.527	neutral	D	0.545539764	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.