TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7665	23218;23219;23220	chr2:178721026;178721025;178721024	chr2:179585753;179585752;179585751
N2AB	7348	22267;22268;22269	chr2:178721026;178721025;178721024	chr2:179585753;179585752;179585751
N2A	6421	19486;19487;19488	chr2:178721026;178721025;178721024	chr2:179585753;179585752;179585751
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: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-61
• Domain position: 58
• Structural Position: 137
• Q(SASA): 0.3141
• 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
L/F	None	None	0.055	N	0.449	0.118	0.418095516054	gnomAD-4.0.0	1.59249E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43353E-05	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
L/A	0.1536	likely_benign	0.142	benign	-2.308	Highly Destabilizing	0.007	N	0.341	neutral	None	None	None	None	N
L/C	0.356	ambiguous	0.3342	benign	-1.667	Destabilizing	0.356	N	0.527	neutral	None	None	None	None	N
L/D	0.5467	ambiguous	0.5494	ambiguous	-2.123	Highly Destabilizing	0.072	N	0.551	neutral	None	None	None	None	N
L/E	0.2261	likely_benign	0.232	benign	-1.991	Destabilizing	0.016	N	0.435	neutral	None	None	None	None	N
L/F	0.0825	likely_benign	0.0838	benign	-1.481	Destabilizing	0.055	N	0.449	neutral	N	0.49126885	None	None	N
L/G	0.4147	ambiguous	0.4099	ambiguous	-2.774	Highly Destabilizing	0.016	N	0.433	neutral	None	None	None	None	N
L/H	0.1091	likely_benign	0.105	benign	-2.058	Highly Destabilizing	0.214	N	0.572	neutral	None	None	None	None	N
L/I	0.0624	likely_benign	0.062	benign	-1.012	Destabilizing	0.006	N	0.328	neutral	None	None	None	None	N
L/K	0.1389	likely_benign	0.1526	benign	-1.578	Destabilizing	0.016	N	0.422	neutral	None	None	None	None	N
L/M	0.0817	likely_benign	0.0785	benign	-0.936	Destabilizing	0.005	N	0.301	neutral	N	0.485689672	None	None	N
L/N	0.227	likely_benign	0.2348	benign	-1.654	Destabilizing	0.038	N	0.556	neutral	None	None	None	None	N
L/P	0.945	likely_pathogenic	0.9413	pathogenic	-1.419	Destabilizing	0.136	N	0.592	neutral	None	None	None	None	N
L/Q	0.0832	likely_benign	0.0829	benign	-1.68	Destabilizing	0.001	N	0.421	neutral	None	None	None	None	N
L/R	0.0973	likely_benign	0.1034	benign	-1.146	Destabilizing	None	N	0.349	neutral	None	None	None	None	N
L/S	0.1287	likely_benign	0.1259	benign	-2.398	Highly Destabilizing	None	N	0.343	neutral	N	0.376441834	None	None	N
L/T	0.1024	likely_benign	0.0991	benign	-2.13	Highly Destabilizing	None	N	0.249	neutral	None	None	None	None	N
L/V	0.0579	likely_benign	0.0559	benign	-1.419	Destabilizing	None	N	0.119	neutral	N	0.390085922	None	None	N
L/W	0.1651	likely_benign	0.1776	benign	-1.71	Destabilizing	0.828	D	0.579	neutral	D	0.529133805	None	None	N
L/Y	0.2046	likely_benign	0.2086	benign	-1.453	Destabilizing	0.356	N	0.575	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.