TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15763	47512;47513;47514	chr2:178618064;178618063;178618062	chr2:179482791;179482790;179482789
N2AB	14122	42589;42590;42591	chr2:178618064;178618063;178618062	chr2:179482791;179482790;179482789
N2A	13195	39808;39809;39810	chr2:178618064;178618063;178618062	chr2:179482791;179482790;179482789
N2B	6698	20317;20318;20319	chr2:178618064;178618063;178618062	chr2:179482791;179482790;179482789
Novex-1	6823	20692;20693;20694	chr2:178618064;178618063;178618062	chr2:179482791;179482790;179482789
Novex-2	6890	20893;20894;20895	chr2:178618064;178618063;178618062	chr2:179482791;179482790;179482789
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: Fn3-2
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.3627
• 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/V	None	None	0.969	N	0.5	0.163	0.298745278005	gnomAD-4.0.0	1.59467E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86331E-06	0	0
L/W	rs2154209220	None	0.999	N	0.791	0.274	0.62360313169	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
L/A	0.128	likely_benign	0.1265	benign	-1.923	Destabilizing	0.953	D	0.611	neutral	None	None	None	None	N
L/C	0.3663	ambiguous	0.3452	ambiguous	-0.937	Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	N
L/D	0.5097	ambiguous	0.5194	ambiguous	-1.761	Destabilizing	0.986	D	0.809	deleterious	None	None	None	None	N
L/E	0.163	likely_benign	0.1747	benign	-1.749	Destabilizing	0.91	D	0.767	deleterious	None	None	None	None	N
L/F	0.1295	likely_benign	0.1352	benign	-1.344	Destabilizing	0.997	D	0.698	prob.neutral	N	0.480474146	None	None	N
L/G	0.2603	likely_benign	0.2587	benign	-2.262	Highly Destabilizing	0.986	D	0.797	deleterious	None	None	None	None	N
L/H	0.1628	likely_benign	0.1639	benign	-1.605	Destabilizing	0.998	D	0.805	deleterious	None	None	None	None	N
L/I	0.0944	likely_benign	0.0908	benign	-1.04	Destabilizing	0.976	D	0.513	neutral	None	None	None	None	N
L/K	0.1101	likely_benign	0.1152	benign	-1.449	Destabilizing	0.973	D	0.761	deleterious	None	None	None	None	N
L/M	0.0934	likely_benign	0.0931	benign	-0.676	Destabilizing	0.991	D	0.7	prob.neutral	N	0.480700739	None	None	N
L/N	0.2409	likely_benign	0.2362	benign	-1.199	Destabilizing	0.986	D	0.817	deleterious	None	None	None	None	N
L/P	0.6713	likely_pathogenic	0.6435	pathogenic	-1.307	Destabilizing	0.993	D	0.823	deleterious	None	None	None	None	N
L/Q	0.0685	likely_benign	0.0716	benign	-1.389	Destabilizing	0.214	N	0.502	neutral	None	None	None	None	N
L/R	0.0908	likely_benign	0.0974	benign	-0.81	Destabilizing	0.973	D	0.797	deleterious	None	None	None	None	N
L/S	0.1403	likely_benign	0.1427	benign	-1.73	Destabilizing	0.982	D	0.754	deleterious	N	0.457181539	None	None	N
L/T	0.1235	likely_benign	0.1195	benign	-1.618	Destabilizing	0.986	D	0.761	deleterious	None	None	None	None	N
L/V	0.0763	likely_benign	0.0757	benign	-1.307	Destabilizing	0.969	D	0.5	neutral	N	0.472658178	None	None	N
L/W	0.2375	likely_benign	0.2437	benign	-1.494	Destabilizing	0.999	D	0.791	deleterious	N	0.516579503	None	None	N
L/Y	0.2611	likely_benign	0.2589	benign	-1.306	Destabilizing	0.998	D	0.817	deleterious	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.