TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9107	27544;27545;27546	chr2:178712706;178712705;178712704	chr2:179577433;179577432;179577431
N2AB	8790	26593;26594;26595	chr2:178712706;178712705;178712704	chr2:179577433;179577432;179577431
N2A	7863	23812;23813;23814	chr2:178712706;178712705;178712704	chr2:179577433;179577432;179577431
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: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-76
• Domain position: 89
• Structural Position: 175
• Q(SASA): 0.4623
• 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
Y/C	None	None	0.828	N	0.339	0.196	0.515430650102	gnomAD-4.0.0	1.59375E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86459E-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
Y/A	0.2583	likely_benign	0.2005	benign	-1.771	Destabilizing	0.016	N	0.335	neutral	None	None	None	None	N
Y/C	0.1293	likely_benign	0.1037	benign	-0.328	Destabilizing	0.828	D	0.339	neutral	N	0.492442286	None	None	N
Y/D	0.1491	likely_benign	0.1183	benign	0.027	Stabilizing	0.055	N	0.455	neutral	N	0.416963092	None	None	N
Y/E	0.3447	ambiguous	0.2744	benign	0.066	Stabilizing	0.072	N	0.405	neutral	None	None	None	None	N
Y/F	0.0753	likely_benign	0.0751	benign	-0.834	Destabilizing	None	N	0.089	neutral	N	0.35822422	None	None	N
Y/G	0.2848	likely_benign	0.2311	benign	-2.052	Highly Destabilizing	0.016	N	0.41	neutral	None	None	None	None	N
Y/H	0.0845	likely_benign	0.0683	benign	-0.633	Destabilizing	None	N	0.141	neutral	N	0.420811474	None	None	N
Y/I	0.2487	likely_benign	0.1986	benign	-0.962	Destabilizing	0.038	N	0.409	neutral	None	None	None	None	N
Y/K	0.3248	likely_benign	0.255	benign	-0.526	Destabilizing	0.038	N	0.437	neutral	None	None	None	None	N
Y/L	0.2516	likely_benign	0.1976	benign	-0.962	Destabilizing	0.016	N	0.343	neutral	None	None	None	None	N
Y/M	0.4004	ambiguous	0.3398	benign	-0.564	Destabilizing	0.356	N	0.36	neutral	None	None	None	None	N
Y/N	0.0841	likely_benign	0.0722	benign	-0.65	Destabilizing	0.029	N	0.425	neutral	N	0.398030615	None	None	N
Y/P	0.849	likely_pathogenic	0.7981	pathogenic	-1.221	Destabilizing	0.356	N	0.423	neutral	None	None	None	None	N
Y/Q	0.2131	likely_benign	0.1603	benign	-0.632	Destabilizing	0.072	N	0.42	neutral	None	None	None	None	N
Y/R	0.1998	likely_benign	0.1476	benign	-0.116	Destabilizing	0.072	N	0.411	neutral	None	None	None	None	N
Y/S	0.0942	likely_benign	0.0794	benign	-1.199	Destabilizing	None	N	0.182	neutral	N	0.386466827	None	None	N
Y/T	0.1864	likely_benign	0.1477	benign	-1.068	Destabilizing	0.016	N	0.391	neutral	None	None	None	None	N
Y/V	0.204	likely_benign	0.168	benign	-1.221	Destabilizing	0.016	N	0.358	neutral	None	None	None	None	N
Y/W	0.371	ambiguous	0.3079	benign	-0.598	Destabilizing	0.356	N	0.391	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.