TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18051	54376;54377;54378	chr2:178605026;178605025;178605024	chr2:179469753;179469752;179469751
N2AB	16410	49453;49454;49455	chr2:178605026;178605025;178605024	chr2:179469753;179469752;179469751
N2A	15483	46672;46673;46674	chr2:178605026;178605025;178605024	chr2:179469753;179469752;179469751
N2B	8986	27181;27182;27183	chr2:178605026;178605025;178605024	chr2:179469753;179469752;179469751
Novex-1	9111	27556;27557;27558	chr2:178605026;178605025;178605024	chr2:179469753;179469752;179469751
Novex-2	9178	27757;27758;27759	chr2:178605026;178605025;178605024	chr2:179469753;179469752;179469751
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-114
• Domain position: 84
• Structural Position: 163
• Q(SASA): 0.4556
• Predicted PPI site: I

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/R	rs771364277	0.28	0.994	N	0.674	0.567	0.810086806081	gnomAD-2.1.1	4.1E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	9.05E-06	0
L/R	rs771364277	0.28	0.994	N	0.674	0.567	0.810086806081	gnomAD-4.0.0	1.37559E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.8065E-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	0.5746	likely_pathogenic	0.5609	ambiguous	-0.423	Destabilizing	0.97	D	0.494	neutral	None	None	None	None	I
L/C	0.7403	likely_pathogenic	0.746	pathogenic	-0.786	Destabilizing	1.0	D	0.587	neutral	None	None	None	None	I
L/D	0.9512	likely_pathogenic	0.9384	pathogenic	-0.191	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	I
L/E	0.8287	likely_pathogenic	0.7985	pathogenic	-0.287	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	I
L/F	0.3907	ambiguous	0.3388	benign	-0.63	Destabilizing	0.151	N	0.27	neutral	N	0.459292504	None	None	I
L/G	0.8292	likely_pathogenic	0.8104	pathogenic	-0.512	Destabilizing	0.996	D	0.668	neutral	None	None	None	None	I
L/H	0.5763	likely_pathogenic	0.5237	ambiguous	0.07	Stabilizing	1.0	D	0.7	prob.neutral	N	0.48886605	None	None	I
L/I	0.2671	likely_benign	0.2754	benign	-0.311	Destabilizing	0.925	D	0.399	neutral	N	0.480475853	None	None	I
L/K	0.634	likely_pathogenic	0.6317	pathogenic	-0.306	Destabilizing	0.996	D	0.618	neutral	None	None	None	None	I
L/M	0.2239	likely_benign	0.2179	benign	-0.56	Destabilizing	0.559	D	0.289	neutral	None	None	None	None	I
L/N	0.7342	likely_pathogenic	0.7064	pathogenic	-0.161	Destabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	I
L/P	0.956	likely_pathogenic	0.9566	pathogenic	-0.321	Destabilizing	0.998	D	0.7	prob.neutral	N	0.512688263	None	None	I
L/Q	0.5013	ambiguous	0.4636	ambiguous	-0.339	Destabilizing	0.996	D	0.67	neutral	None	None	None	None	I
L/R	0.5374	ambiguous	0.5334	ambiguous	0.14	Stabilizing	0.994	D	0.674	neutral	N	0.505123581	None	None	I
L/S	0.7297	likely_pathogenic	0.6861	pathogenic	-0.545	Destabilizing	0.996	D	0.587	neutral	None	None	None	None	I
L/T	0.6674	likely_pathogenic	0.6473	pathogenic	-0.542	Destabilizing	0.996	D	0.49	neutral	None	None	None	None	I
L/V	0.2743	likely_benign	0.2783	benign	-0.321	Destabilizing	0.835	D	0.449	neutral	N	0.459252432	None	None	I
L/W	0.5972	likely_pathogenic	0.5557	ambiguous	-0.652	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
L/Y	0.6418	likely_pathogenic	0.5877	pathogenic	-0.412	Destabilizing	0.983	D	0.535	neutral	None	None	None	None	I

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.