TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24970	75133;75134;75135	chr2:178571224;178571223;178571222	chr2:179435951;179435950;179435949
N2AB	23329	70210;70211;70212	chr2:178571224;178571223;178571222	chr2:179435951;179435950;179435949
N2A	22402	67429;67430;67431	chr2:178571224;178571223;178571222	chr2:179435951;179435950;179435949
N2B	15905	47938;47939;47940	chr2:178571224;178571223;178571222	chr2:179435951;179435950;179435949
Novex-1	16030	48313;48314;48315	chr2:178571224;178571223;178571222	chr2:179435951;179435950;179435949
Novex-2	16097	48514;48515;48516	chr2:178571224;178571223;178571222	chr2:179435951;179435950;179435949
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-69
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.0867
• 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
T/I	rs779917922	0.64	0.016	N	0.515	0.156	0.176091768786	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	0	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
T/A	0.0824	likely_benign	0.0803	benign	-0.973	Destabilizing	0.002	N	0.223	neutral	N	0.418162666	None	None	N
T/C	0.3563	ambiguous	0.327	benign	-0.561	Destabilizing	0.92	D	0.781	deleterious	None	None	None	None	N
T/D	0.7664	likely_pathogenic	0.7661	pathogenic	-0.853	Destabilizing	0.92	D	0.769	deleterious	None	None	None	None	N
T/E	0.7255	likely_pathogenic	0.7281	pathogenic	-0.62	Destabilizing	0.617	D	0.737	prob.delet.	None	None	None	None	N
T/F	0.4963	ambiguous	0.4793	ambiguous	-0.81	Destabilizing	0.85	D	0.805	deleterious	None	None	None	None	N
T/G	0.3478	ambiguous	0.3197	benign	-1.41	Destabilizing	0.447	N	0.742	deleterious	None	None	None	None	N
T/H	0.6787	likely_pathogenic	0.6516	pathogenic	-1.44	Destabilizing	0.992	D	0.816	deleterious	None	None	None	None	N
T/I	0.2207	likely_benign	0.2135	benign	0.181	Stabilizing	0.016	N	0.515	neutral	N	0.382737796	None	None	N
T/K	0.8148	likely_pathogenic	0.8023	pathogenic	-0.009	Destabilizing	0.549	D	0.733	prob.delet.	N	0.467240955	None	None	N
T/L	0.1722	likely_benign	0.1626	benign	0.181	Stabilizing	0.25	N	0.623	neutral	None	None	None	None	N
T/M	0.1192	likely_benign	0.1181	benign	0.081	Stabilizing	0.92	D	0.774	deleterious	None	None	None	None	N
T/N	0.3382	likely_benign	0.3197	benign	-0.837	Destabilizing	0.92	D	0.693	prob.neutral	None	None	None	None	N
T/P	0.5903	likely_pathogenic	0.5583	ambiguous	-0.172	Destabilizing	0.896	D	0.787	deleterious	N	0.508917956	None	None	N
T/Q	0.6572	likely_pathogenic	0.6391	pathogenic	-0.517	Destabilizing	0.92	D	0.789	deleterious	None	None	None	None	N
T/R	0.7851	likely_pathogenic	0.7675	pathogenic	-0.373	Destabilizing	0.81	D	0.782	deleterious	N	0.47859726	None	None	N
T/S	0.1445	likely_benign	0.1455	benign	-1.175	Destabilizing	0.201	N	0.587	neutral	N	0.486579814	None	None	N
T/V	0.1387	likely_benign	0.1308	benign	-0.172	Destabilizing	0.002	N	0.227	neutral	None	None	None	None	N
T/W	0.8937	likely_pathogenic	0.8771	pathogenic	-0.928	Destabilizing	0.992	D	0.791	deleterious	None	None	None	None	N
T/Y	0.6075	likely_pathogenic	0.5681	pathogenic	-0.497	Destabilizing	0.92	D	0.814	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.