TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25174	75745;75746;75747	chr2:178570612;178570611;178570610	chr2:179435339;179435338;179435337
N2AB	23533	70822;70823;70824	chr2:178570612;178570611;178570610	chr2:179435339;179435338;179435337
N2A	22606	68041;68042;68043	chr2:178570612;178570611;178570610	chr2:179435339;179435338;179435337
N2B	16109	48550;48551;48552	chr2:178570612;178570611;178570610	chr2:179435339;179435338;179435337
Novex-1	16234	48925;48926;48927	chr2:178570612;178570611;178570610	chr2:179435339;179435338;179435337
Novex-2	16301	49126;49127;49128	chr2:178570612;178570611;178570610	chr2:179435339;179435338;179435337
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-134
• Domain position: 64
• Structural Position: 144
• Q(SASA): 0.0981
• 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
A/V	rs772038176	-0.505	0.955	N	0.659	0.289	0.637886457206	gnomAD-2.1.1	1.07E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.35E-05	0
A/V	rs772038176	-0.505	0.955	N	0.659	0.289	0.637886457206	gnomAD-4.0.0	4.77585E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.57775E-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
A/C	0.4432	ambiguous	0.4468	ambiguous	-1.842	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
A/D	0.9664	likely_pathogenic	0.9726	pathogenic	-2.579	Highly Destabilizing	0.995	D	0.775	deleterious	None	None	None	None	N
A/E	0.9616	likely_pathogenic	0.9732	pathogenic	-2.524	Highly Destabilizing	0.993	D	0.767	deleterious	D	0.544572041	None	None	N
A/F	0.9032	likely_pathogenic	0.9229	pathogenic	-1.194	Destabilizing	0.998	D	0.795	deleterious	None	None	None	None	N
A/G	0.3176	likely_benign	0.3213	benign	-1.526	Destabilizing	0.977	D	0.64	neutral	D	0.526214296	None	None	N
A/H	0.9725	likely_pathogenic	0.9791	pathogenic	-1.514	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
A/I	0.4783	ambiguous	0.5167	ambiguous	-0.486	Destabilizing	0.995	D	0.784	deleterious	None	None	None	None	N
A/K	0.9859	likely_pathogenic	0.9909	pathogenic	-1.446	Destabilizing	0.995	D	0.769	deleterious	None	None	None	None	N
A/L	0.502	ambiguous	0.5564	ambiguous	-0.486	Destabilizing	0.966	D	0.675	neutral	None	None	None	None	N
A/M	0.5615	ambiguous	0.6087	pathogenic	-0.747	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
A/N	0.8846	likely_pathogenic	0.9048	pathogenic	-1.588	Destabilizing	0.995	D	0.772	deleterious	None	None	None	None	N
A/P	0.8084	likely_pathogenic	0.8481	pathogenic	-0.693	Destabilizing	0.997	D	0.791	deleterious	N	0.502273918	None	None	N
A/Q	0.9505	likely_pathogenic	0.9636	pathogenic	-1.707	Destabilizing	0.998	D	0.794	deleterious	None	None	None	None	N
A/R	0.9672	likely_pathogenic	0.9777	pathogenic	-1.158	Destabilizing	0.998	D	0.784	deleterious	None	None	None	None	N
A/S	0.1653	likely_benign	0.1606	benign	-1.928	Destabilizing	0.955	D	0.589	neutral	N	0.519210386	None	None	N
A/T	0.1427	likely_benign	0.1473	benign	-1.778	Destabilizing	0.568	D	0.415	neutral	D	0.53240897	None	None	N
A/V	0.1927	likely_benign	0.2073	benign	-0.693	Destabilizing	0.955	D	0.659	neutral	N	0.500058904	None	None	N
A/W	0.9894	likely_pathogenic	0.992	pathogenic	-1.608	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
A/Y	0.9655	likely_pathogenic	0.975	pathogenic	-1.179	Destabilizing	1.0	D	0.785	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.