TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30978	93157;93158;93159	chr2:178548694;178548693;178548692	chr2:179413421;179413420;179413419
N2AB	29337	88234;88235;88236	chr2:178548694;178548693;178548692	chr2:179413421;179413420;179413419
N2A	28410	85453;85454;85455	chr2:178548694;178548693;178548692	chr2:179413421;179413420;179413419
N2B	21913	65962;65963;65964	chr2:178548694;178548693;178548692	chr2:179413421;179413420;179413419
Novex-1	22038	66337;66338;66339	chr2:178548694;178548693;178548692	chr2:179413421;179413420;179413419
Novex-2	22105	66538;66539;66540	chr2:178548694;178548693;178548692	chr2:179413421;179413420;179413419
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-150
• Domain position: 52
• Structural Position: 135
• Q(SASA): 0.1887
• 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
F/L	None	None	0.013	N	0.155	0.174	0.310458034454	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
F/A	0.7455	likely_pathogenic	0.7498	pathogenic	-2.327	Highly Destabilizing	0.739	D	0.473	neutral	None	None	None	None	N
F/C	0.4314	ambiguous	0.4026	ambiguous	-1.13	Destabilizing	0.999	D	0.506	neutral	N	0.484092161	None	None	N
F/D	0.9255	likely_pathogenic	0.9164	pathogenic	-1.774	Destabilizing	0.932	D	0.551	neutral	None	None	None	None	N
F/E	0.9384	likely_pathogenic	0.929	pathogenic	-1.653	Destabilizing	0.873	D	0.55	neutral	None	None	None	None	N
F/G	0.8972	likely_pathogenic	0.8905	pathogenic	-2.695	Highly Destabilizing	0.932	D	0.555	neutral	None	None	None	None	N
F/H	0.6149	likely_pathogenic	0.5846	pathogenic	-1.178	Destabilizing	0.99	D	0.475	neutral	None	None	None	None	N
F/I	0.4566	ambiguous	0.4279	ambiguous	-1.18	Destabilizing	0.838	D	0.29	neutral	N	0.463426101	None	None	N
F/K	0.9346	likely_pathogenic	0.9233	pathogenic	-1.136	Destabilizing	0.873	D	0.533	neutral	None	None	None	None	N
F/L	0.9381	likely_pathogenic	0.9352	pathogenic	-1.18	Destabilizing	0.013	N	0.155	neutral	N	0.436356929	None	None	N
F/M	0.7086	likely_pathogenic	0.6969	pathogenic	-0.811	Destabilizing	0.98	D	0.419	neutral	None	None	None	None	N
F/N	0.7853	likely_pathogenic	0.7728	pathogenic	-1.272	Destabilizing	0.932	D	0.558	neutral	None	None	None	None	N
F/P	0.9979	likely_pathogenic	0.9974	pathogenic	-1.562	Destabilizing	0.99	D	0.554	neutral	None	None	None	None	N
F/Q	0.8731	likely_pathogenic	0.858	pathogenic	-1.354	Destabilizing	0.348	N	0.436	neutral	None	None	None	None	N
F/R	0.8556	likely_pathogenic	0.8353	pathogenic	-0.565	Destabilizing	0.98	D	0.554	neutral	None	None	None	None	N
F/S	0.5488	ambiguous	0.5526	ambiguous	-2.022	Highly Destabilizing	0.288	N	0.33	neutral	N	0.373190885	None	None	N
F/T	0.7114	likely_pathogenic	0.7078	pathogenic	-1.805	Destabilizing	0.873	D	0.521	neutral	None	None	None	None	N
F/V	0.3965	ambiguous	0.3726	ambiguous	-1.562	Destabilizing	0.681	D	0.435	neutral	N	0.445784489	None	None	N
F/W	0.6481	likely_pathogenic	0.6001	pathogenic	-0.463	Destabilizing	0.997	D	0.433	neutral	None	None	None	None	N
F/Y	0.1382	likely_benign	0.1346	benign	-0.659	Destabilizing	0.122	N	0.231	neutral	N	0.393510229	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.