TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24463	73612;73613;73614	chr2:178572745;178572744;178572743	chr2:179437472;179437471;179437470
N2AB	22822	68689;68690;68691	chr2:178572745;178572744;178572743	chr2:179437472;179437471;179437470
N2A	21895	65908;65909;65910	chr2:178572745;178572744;178572743	chr2:179437472;179437471;179437470
N2B	15398	46417;46418;46419	chr2:178572745;178572744;178572743	chr2:179437472;179437471;179437470
Novex-1	15523	46792;46793;46794	chr2:178572745;178572744;178572743	chr2:179437472;179437471;179437470
Novex-2	15590	46993;46994;46995	chr2:178572745;178572744;178572743	chr2:179437472;179437471;179437470
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-132
• Domain position: 33
• Structural Position: 49
• Q(SASA): 0.2748
• 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
A/D	None	None	0.117	N	0.583	0.129	0.338592109245	gnomAD-4.0.0	2.05294E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69875E-06	0	0
A/V	None	None	0.062	N	0.446	0.177	0.218845423259	gnomAD-4.0.0	6.84313E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99583E-07	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	0.2682	likely_benign	0.279	benign	-0.685	Destabilizing	0.555	D	0.503	neutral	None	None	None	None	I
A/D	0.2066	likely_benign	0.2262	benign	-0.882	Destabilizing	0.117	N	0.583	neutral	N	0.45738191	None	None	I
A/E	0.1537	likely_benign	0.1559	benign	-0.805	Destabilizing	0.149	N	0.527	neutral	None	None	None	None	I
A/F	0.1904	likely_benign	0.2033	benign	-0.607	Destabilizing	0.555	D	0.632	neutral	None	None	None	None	I
A/G	0.1084	likely_benign	0.1173	benign	-1.114	Destabilizing	0.027	N	0.457	neutral	N	0.376574254	None	None	I
A/H	0.2552	likely_benign	0.2724	benign	-1.378	Destabilizing	0.935	D	0.622	neutral	None	None	None	None	I
A/I	0.1327	likely_benign	0.1376	benign	0.188	Stabilizing	0.081	N	0.566	neutral	None	None	None	None	I
A/K	0.2475	likely_benign	0.2544	benign	-0.871	Destabilizing	0.149	N	0.53	neutral	None	None	None	None	I
A/L	0.0978	likely_benign	0.1022	benign	0.188	Stabilizing	0.081	N	0.517	neutral	None	None	None	None	I
A/M	0.1154	likely_benign	0.1163	benign	0.063	Stabilizing	0.555	D	0.564	neutral	None	None	None	None	I
A/N	0.1318	likely_benign	0.1426	benign	-0.761	Destabilizing	0.149	N	0.583	neutral	None	None	None	None	I
A/P	0.8331	likely_pathogenic	0.8279	pathogenic	-0.075	Destabilizing	0.211	N	0.563	neutral	N	0.45738191	None	None	I
A/Q	0.1793	likely_benign	0.1887	benign	-0.726	Destabilizing	0.38	N	0.581	neutral	None	None	None	None	I
A/R	0.2353	likely_benign	0.2422	benign	-0.825	Destabilizing	0.38	N	0.564	neutral	None	None	None	None	I
A/S	0.0683	likely_benign	0.0709	benign	-1.238	Destabilizing	None	N	0.182	neutral	N	0.302441855	None	None	I
A/T	0.0588	likely_benign	0.0584	benign	-1.033	Destabilizing	None	N	0.171	neutral	N	0.348616862	None	None	I
A/V	0.088	likely_benign	0.0891	benign	-0.075	Destabilizing	0.062	N	0.446	neutral	N	0.375803463	None	None	I
A/W	0.549	ambiguous	0.5855	pathogenic	-1.13	Destabilizing	0.935	D	0.661	neutral	None	None	None	None	I
A/Y	0.2885	likely_benign	0.3082	benign	-0.599	Destabilizing	0.555	D	0.645	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.