TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7763	23512;23513;23514	chr2:178720475;178720474;178720473	chr2:179585202;179585201;179585200
N2AB	7446	22561;22562;22563	chr2:178720475;178720474;178720473	chr2:179585202;179585201;179585200
N2A	6519	19780;19781;19782	chr2:178720475;178720474;178720473	chr2:179585202;179585201;179585200
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: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-62
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.6699
• 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
N/S	None	None	None	N	0.069	0.057	0.0297737177859	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-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
N/A	0.2192	likely_benign	0.2151	benign	-0.652	Destabilizing	0.002	N	0.297	neutral	None	None	None	None	N
N/C	0.3191	likely_benign	0.2889	benign	0.168	Stabilizing	0.867	D	0.318	neutral	None	None	None	None	N
N/D	0.2064	likely_benign	0.1809	benign	-0.501	Destabilizing	0.017	N	0.206	neutral	N	0.47233272	None	None	N
N/E	0.5373	ambiguous	0.501	ambiguous	-0.469	Destabilizing	0.016	N	0.217	neutral	None	None	None	None	N
N/F	0.5072	ambiguous	0.4623	ambiguous	-0.707	Destabilizing	0.502	D	0.375	neutral	None	None	None	None	N
N/G	0.2187	likely_benign	0.2262	benign	-0.922	Destabilizing	0.038	N	0.253	neutral	None	None	None	None	N
N/H	0.0893	likely_benign	0.078	benign	-0.852	Destabilizing	0.001	N	0.199	neutral	N	0.50887231	None	None	N
N/I	0.3552	ambiguous	0.3137	benign	0.001	Stabilizing	0.366	N	0.387	neutral	N	0.472460605	None	None	N
N/K	0.3872	ambiguous	0.3505	ambiguous	-0.125	Destabilizing	0.001	N	0.079	neutral	N	0.431006172	None	None	N
N/L	0.2479	likely_benign	0.2288	benign	0.001	Stabilizing	0.097	N	0.382	neutral	None	None	None	None	N
N/M	0.3467	ambiguous	0.3248	benign	0.606	Stabilizing	0.699	D	0.33	neutral	None	None	None	None	N
N/P	0.7899	likely_pathogenic	0.7526	pathogenic	-0.188	Destabilizing	0.141	N	0.385	neutral	None	None	None	None	N
N/Q	0.2963	likely_benign	0.2863	benign	-0.802	Destabilizing	0.097	N	0.255	neutral	None	None	None	None	N
N/R	0.4183	ambiguous	0.3836	ambiguous	-0.051	Destabilizing	0.001	N	0.151	neutral	None	None	None	None	N
N/S	0.0749	likely_benign	0.0749	benign	-0.612	Destabilizing	None	N	0.069	neutral	N	0.430832814	None	None	N
N/T	0.1431	likely_benign	0.1424	benign	-0.409	Destabilizing	0.006	N	0.212	neutral	N	0.50887231	None	None	N
N/V	0.3457	ambiguous	0.3197	benign	-0.188	Destabilizing	0.009	N	0.421	neutral	None	None	None	None	N
N/W	0.7882	likely_pathogenic	0.7381	pathogenic	-0.524	Destabilizing	0.002	N	0.251	neutral	None	None	None	None	N
N/Y	0.185	likely_benign	0.1562	benign	-0.298	Destabilizing	0.276	N	0.383	neutral	N	0.486930782	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.