TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29360	88303;88304;88305	chr2:178557076;178557075;178557074	chr2:179421803;179421802;179421801
N2AB	27719	83380;83381;83382	chr2:178557076;178557075;178557074	chr2:179421803;179421802;179421801
N2A	26792	80599;80600;80601	chr2:178557076;178557075;178557074	chr2:179421803;179421802;179421801
N2B	20295	61108;61109;61110	chr2:178557076;178557075;178557074	chr2:179421803;179421802;179421801
Novex-1	20420	61483;61484;61485	chr2:178557076;178557075;178557074	chr2:179421803;179421802;179421801
Novex-2	20487	61684;61685;61686	chr2:178557076;178557075;178557074	chr2:179421803;179421802;179421801
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-102
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.3262
• 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
A/G	None	None	0.625	N	0.347	0.217	0.197625483188	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
A/C	0.4588	ambiguous	0.4274	ambiguous	-0.791	Destabilizing	0.998	D	0.357	neutral	None	None	None	None	N
A/D	0.2697	likely_benign	0.2163	benign	-0.779	Destabilizing	0.669	D	0.459	neutral	N	0.454411467	None	None	N
A/E	0.2318	likely_benign	0.1955	benign	-0.922	Destabilizing	0.842	D	0.389	neutral	None	None	None	None	N
A/F	0.3445	ambiguous	0.3048	benign	-0.93	Destabilizing	0.037	N	0.262	neutral	None	None	None	None	N
A/G	0.1507	likely_benign	0.1424	benign	-0.475	Destabilizing	0.625	D	0.347	neutral	N	0.424648708	None	None	N
A/H	0.4514	ambiguous	0.4226	ambiguous	-0.45	Destabilizing	0.974	D	0.454	neutral	None	None	None	None	N
A/I	0.174	likely_benign	0.1588	benign	-0.414	Destabilizing	0.904	D	0.387	neutral	None	None	None	None	N
A/K	0.4286	ambiguous	0.3738	ambiguous	-0.87	Destabilizing	0.842	D	0.398	neutral	None	None	None	None	N
A/L	0.1342	likely_benign	0.1308	benign	-0.414	Destabilizing	0.728	D	0.385	neutral	None	None	None	None	N
A/M	0.2041	likely_benign	0.1945	benign	-0.487	Destabilizing	0.993	D	0.377	neutral	None	None	None	None	N
A/N	0.1955	likely_benign	0.1872	benign	-0.521	Destabilizing	0.067	N	0.23	neutral	None	None	None	None	N
A/P	0.1598	likely_benign	0.1545	benign	-0.377	Destabilizing	0.966	D	0.41	neutral	N	0.472285152	None	None	N
A/Q	0.2924	likely_benign	0.2752	benign	-0.811	Destabilizing	0.974	D	0.404	neutral	None	None	None	None	N
A/R	0.4084	ambiguous	0.3522	ambiguous	-0.328	Destabilizing	0.974	D	0.385	neutral	None	None	None	None	N
A/S	0.0888	likely_benign	0.089	benign	-0.692	Destabilizing	0.136	N	0.145	neutral	N	0.451813879	None	None	N
A/T	0.0834	likely_benign	0.0832	benign	-0.762	Destabilizing	0.669	D	0.344	neutral	N	0.417701306	None	None	N
A/V	0.1037	likely_benign	0.0947	benign	-0.377	Destabilizing	0.801	D	0.325	neutral	N	0.436865857	None	None	N
A/W	0.7429	likely_pathogenic	0.6859	pathogenic	-1.077	Destabilizing	0.998	D	0.507	neutral	None	None	None	None	N
A/Y	0.451	ambiguous	0.4122	ambiguous	-0.75	Destabilizing	0.904	D	0.491	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.