TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26016	78271;78272;78273	chr2:178568086;178568085;178568084	chr2:179432813;179432812;179432811
N2AB	24375	73348;73349;73350	chr2:178568086;178568085;178568084	chr2:179432813;179432812;179432811
N2A	23448	70567;70568;70569	chr2:178568086;178568085;178568084	chr2:179432813;179432812;179432811
N2B	16951	51076;51077;51078	chr2:178568086;178568085;178568084	chr2:179432813;179432812;179432811
Novex-1	17076	51451;51452;51453	chr2:178568086;178568085;178568084	chr2:179432813;179432812;179432811
Novex-2	17143	51652;51653;51654	chr2:178568086;178568085;178568084	chr2:179432813;179432812;179432811
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-77
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.662
• 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
N/T	None	None	0.349	N	0.368	0.092	0.240491677333	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.9375E-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
N/A	0.1956	likely_benign	0.1778	benign	-0.407	Destabilizing	0.415	N	0.455	neutral	None	None	None	None	I
N/C	0.1823	likely_benign	0.1722	benign	0.379	Stabilizing	0.996	D	0.565	neutral	None	None	None	None	I
N/D	0.2021	likely_benign	0.2065	benign	-0.026	Destabilizing	0.722	D	0.407	neutral	N	0.44728792	None	None	I
N/E	0.4872	ambiguous	0.4927	ambiguous	-0.061	Destabilizing	0.775	D	0.376	neutral	None	None	None	None	I
N/F	0.3703	ambiguous	0.3656	ambiguous	-0.78	Destabilizing	0.961	D	0.585	neutral	None	None	None	None	I
N/G	0.2668	likely_benign	0.2612	benign	-0.584	Destabilizing	0.415	N	0.399	neutral	None	None	None	None	I
N/H	0.1049	likely_benign	0.1002	benign	-0.685	Destabilizing	0.949	D	0.407	neutral	N	0.490790768	None	None	I
N/I	0.159	likely_benign	0.1521	benign	-0.028	Destabilizing	0.949	D	0.593	neutral	N	0.514763706	None	None	I
N/K	0.4751	ambiguous	0.4984	ambiguous	0.082	Stabilizing	0.565	D	0.375	neutral	N	0.486942386	None	None	I
N/L	0.1897	likely_benign	0.1806	benign	-0.028	Destabilizing	0.775	D	0.521	neutral	None	None	None	None	I
N/M	0.2506	likely_benign	0.2401	benign	0.443	Stabilizing	0.996	D	0.549	neutral	None	None	None	None	I
N/P	0.8792	likely_pathogenic	0.8894	pathogenic	-0.128	Destabilizing	0.961	D	0.547	neutral	None	None	None	None	I
N/Q	0.3535	ambiguous	0.3424	ambiguous	-0.407	Destabilizing	0.923	D	0.378	neutral	None	None	None	None	I
N/R	0.4997	ambiguous	0.5217	ambiguous	0.13	Stabilizing	0.923	D	0.363	neutral	None	None	None	None	I
N/S	0.0642	likely_benign	0.0625	benign	-0.14	Destabilizing	0.005	N	0.071	neutral	N	0.437495001	None	None	I
N/T	0.1014	likely_benign	0.0895	benign	-0.032	Destabilizing	0.349	N	0.368	neutral	N	0.51647586	None	None	I
N/V	0.1692	likely_benign	0.1627	benign	-0.128	Destabilizing	0.923	D	0.507	neutral	None	None	None	None	I
N/W	0.7263	likely_pathogenic	0.7462	pathogenic	-0.741	Destabilizing	0.996	D	0.677	prob.neutral	None	None	None	None	I
N/Y	0.1448	likely_benign	0.1609	benign	-0.481	Destabilizing	0.983	D	0.566	neutral	N	0.475167955	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.