TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27789	83590;83591;83592	chr2:178562767;178562766;178562765	chr2:179427494;179427493;179427492
N2AB	26148	78667;78668;78669	chr2:178562767;178562766;178562765	chr2:179427494;179427493;179427492
N2A	25221	75886;75887;75888	chr2:178562767;178562766;178562765	chr2:179427494;179427493;179427492
N2B	18724	56395;56396;56397	chr2:178562767;178562766;178562765	chr2:179427494;179427493;179427492
Novex-1	18849	56770;56771;56772	chr2:178562767;178562766;178562765	chr2:179427494;179427493;179427492
Novex-2	18916	56971;56972;56973	chr2:178562767;178562766;178562765	chr2:179427494;179427493;179427492
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-90
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.4729
• 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
P/A	rs1704156538	None	0.008	N	0.363	0.204	0.231873229951	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
P/A	rs1704156538	None	0.008	N	0.363	0.204	0.231873229951	gnomAD-4.0.0	6.57436E-06	None	None	None	None	I	None	2.41359E-05	0	None	0	0	None	0	0	0	0	0
P/T	rs1704156538	None	0.805	N	0.628	0.354	0.407767136052	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	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
P/A	0.0796	likely_benign	0.0805	benign	-1.833	Destabilizing	0.008	N	0.363	neutral	N	0.484833162	None	None	I
P/C	0.5995	likely_pathogenic	0.5843	pathogenic	-1.242	Destabilizing	0.997	D	0.747	deleterious	None	None	None	None	I
P/D	0.7385	likely_pathogenic	0.7787	pathogenic	-2.232	Highly Destabilizing	0.604	D	0.657	neutral	None	None	None	None	I
P/E	0.4659	ambiguous	0.5185	ambiguous	-2.098	Highly Destabilizing	0.828	D	0.656	neutral	None	None	None	None	I
P/F	0.5867	likely_pathogenic	0.5987	pathogenic	-1.217	Destabilizing	0.999	D	0.758	deleterious	None	None	None	None	I
P/G	0.453	ambiguous	0.4582	ambiguous	-2.264	Highly Destabilizing	0.816	D	0.575	neutral	None	None	None	None	I
P/H	0.3603	ambiguous	0.3786	ambiguous	-1.81	Destabilizing	0.998	D	0.725	prob.delet.	None	None	None	None	I
P/I	0.2697	likely_benign	0.2553	benign	-0.678	Destabilizing	0.994	D	0.772	deleterious	None	None	None	None	I
P/K	0.5083	ambiguous	0.5566	ambiguous	-1.711	Destabilizing	0.994	D	0.651	neutral	None	None	None	None	I
P/L	0.1121	likely_benign	0.1135	benign	-0.678	Destabilizing	0.991	D	0.713	prob.delet.	N	0.49131728	None	None	I
P/M	0.2109	likely_benign	0.2121	benign	-0.548	Destabilizing	0.999	D	0.722	prob.delet.	None	None	None	None	I
P/N	0.4319	ambiguous	0.4369	ambiguous	-1.809	Destabilizing	0.038	N	0.432	neutral	None	None	None	None	I
P/Q	0.2215	likely_benign	0.242	benign	-1.804	Destabilizing	0.977	D	0.717	prob.delet.	N	0.492722859	None	None	I
P/R	0.4565	ambiguous	0.498	ambiguous	-1.309	Destabilizing	0.991	D	0.741	deleterious	N	0.491063791	None	None	I
P/S	0.1744	likely_benign	0.1761	benign	-2.333	Highly Destabilizing	0.822	D	0.563	neutral	N	0.494101984	None	None	I
P/T	0.1408	likely_benign	0.1348	benign	-2.071	Highly Destabilizing	0.805	D	0.628	neutral	N	0.496001315	None	None	I
P/V	0.1842	likely_benign	0.1815	benign	-1.033	Destabilizing	0.931	D	0.663	neutral	None	None	None	None	I
P/W	0.8445	likely_pathogenic	0.862	pathogenic	-1.595	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
P/Y	0.585	likely_pathogenic	0.5985	pathogenic	-1.233	Destabilizing	1.0	D	0.763	deleterious	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.