TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8132	24619;24620;24621	chr2:178718806;178718805;178718804	chr2:179583533;179583532;179583531
N2AB	7815	23668;23669;23670	chr2:178718806;178718805;178718804	chr2:179583533;179583532;179583531
N2A	6888	20887;20888;20889	chr2:178718806;178718805;178718804	chr2:179583533;179583532;179583531
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: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-66
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.2618
• 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
V/A	None	None	0.042	N	0.315	0.173	0.513787655203	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
V/A	0.1735	likely_benign	0.1882	benign	-1.48	Destabilizing	0.042	N	0.315	neutral	N	0.499491397	None	None	N
V/C	0.6538	likely_pathogenic	0.6824	pathogenic	-1.112	Destabilizing	0.958	D	0.512	neutral	None	None	None	None	N
V/D	0.2881	likely_benign	0.3216	benign	-1.393	Destabilizing	0.175	N	0.628	neutral	D	0.526322786	None	None	N
V/E	0.1867	likely_benign	0.2041	benign	-1.393	Destabilizing	0.124	N	0.563	neutral	None	None	None	None	N
V/F	0.1144	likely_benign	0.1242	benign	-1.165	Destabilizing	0.001	N	0.217	neutral	D	0.529768523	None	None	N
V/G	0.2267	likely_benign	0.2441	benign	-1.79	Destabilizing	0.175	N	0.593	neutral	N	0.506448946	None	None	N
V/H	0.3489	ambiguous	0.3816	ambiguous	-1.327	Destabilizing	0.002	N	0.443	neutral	None	None	None	None	N
V/I	0.0718	likely_benign	0.073	benign	-0.73	Destabilizing	0.001	N	0.156	neutral	N	0.504966079	None	None	N
V/K	0.199	likely_benign	0.2129	benign	-1.139	Destabilizing	0.001	N	0.426	neutral	None	None	None	None	N
V/L	0.1416	likely_benign	0.1462	benign	-0.73	Destabilizing	None	N	0.147	neutral	N	0.488497903	None	None	N
V/M	0.1145	likely_benign	0.1192	benign	-0.636	Destabilizing	0.009	N	0.243	neutral	None	None	None	None	N
V/N	0.2384	likely_benign	0.266	benign	-0.962	Destabilizing	0.22	N	0.627	neutral	None	None	None	None	N
V/P	0.7504	likely_pathogenic	0.7715	pathogenic	-0.946	Destabilizing	0.667	D	0.599	neutral	None	None	None	None	N
V/Q	0.1877	likely_benign	0.2016	benign	-1.156	Destabilizing	0.497	N	0.6	neutral	None	None	None	None	N
V/R	0.1669	likely_benign	0.18	benign	-0.657	Destabilizing	0.124	N	0.629	neutral	None	None	None	None	N
V/S	0.1747	likely_benign	0.1898	benign	-1.496	Destabilizing	0.124	N	0.55	neutral	None	None	None	None	N
V/T	0.1498	likely_benign	0.1636	benign	-1.391	Destabilizing	0.004	N	0.174	neutral	None	None	None	None	N
V/W	0.6217	likely_pathogenic	0.6487	pathogenic	-1.334	Destabilizing	0.958	D	0.587	neutral	None	None	None	None	N
V/Y	0.382	ambiguous	0.4082	ambiguous	-1.037	Destabilizing	0.124	N	0.554	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.