TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29665	89218;89219;89220	chr2:178554118;178554117;178554116	chr2:179418845;179418844;179418843
N2AB	28024	84295;84296;84297	chr2:178554118;178554117;178554116	chr2:179418845;179418844;179418843
N2A	27097	81514;81515;81516	chr2:178554118;178554117;178554116	chr2:179418845;179418844;179418843
N2B	20600	62023;62024;62025	chr2:178554118;178554117;178554116	chr2:179418845;179418844;179418843
Novex-1	20725	62398;62399;62400	chr2:178554118;178554117;178554116	chr2:179418845;179418844;179418843
Novex-2	20792	62599;62600;62601	chr2:178554118;178554117;178554116	chr2:179418845;179418844;179418843
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-104
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.219
• 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
I/L	None	None	0.043	N	0.415	0.166	0.235664433957	gnomAD-4.0.0	6.84187E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99446E-07	0	0
I/R	None	None	0.781	D	0.837	0.545	0.841281731114	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31252E-06	0	0
I/V	rs1700376721	None	0.001	N	0.252	0.082	0.230578612272	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	2.06697E-04	0
I/V	rs1700376721	None	0.001	N	0.252	0.082	0.230578612272	gnomAD-4.0.0	3.09832E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.54275E-06	2.19553E-05	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
I/A	0.8929	likely_pathogenic	0.9341	pathogenic	-2.27	Highly Destabilizing	0.25	N	0.657	neutral	None	None	None	None	I
I/C	0.917	likely_pathogenic	0.9434	pathogenic	-1.631	Destabilizing	0.947	D	0.73	prob.delet.	None	None	None	None	I
I/D	0.9907	likely_pathogenic	0.9948	pathogenic	-1.97	Destabilizing	0.826	D	0.839	deleterious	None	None	None	None	I
I/E	0.9825	likely_pathogenic	0.9896	pathogenic	-1.889	Destabilizing	0.826	D	0.832	deleterious	None	None	None	None	I
I/F	0.7705	likely_pathogenic	0.8485	pathogenic	-1.579	Destabilizing	0.7	D	0.733	prob.delet.	None	None	None	None	I
I/G	0.9781	likely_pathogenic	0.9896	pathogenic	-2.694	Highly Destabilizing	0.826	D	0.835	deleterious	None	None	None	None	I
I/H	0.9828	likely_pathogenic	0.9897	pathogenic	-1.907	Destabilizing	0.982	D	0.805	deleterious	None	None	None	None	I
I/K	0.9733	likely_pathogenic	0.9816	pathogenic	-1.596	Destabilizing	0.781	D	0.831	deleterious	D	0.556394148	None	None	I
I/L	0.294	likely_benign	0.3555	ambiguous	-1.12	Destabilizing	0.043	N	0.415	neutral	N	0.49522762	None	None	I
I/M	0.4659	ambiguous	0.566	pathogenic	-0.941	Destabilizing	0.638	D	0.699	prob.neutral	D	0.544023884	None	None	I
I/N	0.911	likely_pathogenic	0.938	pathogenic	-1.564	Destabilizing	0.935	D	0.838	deleterious	None	None	None	None	I
I/P	0.9098	likely_pathogenic	0.9261	pathogenic	-1.476	Destabilizing	0.826	D	0.839	deleterious	None	None	None	None	I
I/Q	0.9774	likely_pathogenic	0.9867	pathogenic	-1.673	Destabilizing	0.935	D	0.831	deleterious	None	None	None	None	I
I/R	0.9574	likely_pathogenic	0.9713	pathogenic	-1.035	Destabilizing	0.781	D	0.837	deleterious	D	0.556394148	None	None	I
I/S	0.9117	likely_pathogenic	0.9432	pathogenic	-2.282	Highly Destabilizing	0.7	D	0.81	deleterious	None	None	None	None	I
I/T	0.8009	likely_pathogenic	0.8675	pathogenic	-2.067	Highly Destabilizing	0.201	N	0.765	deleterious	D	0.523539772	None	None	I
I/V	0.0753	likely_benign	0.0927	benign	-1.476	Destabilizing	0.001	N	0.252	neutral	N	0.488854902	None	None	I
I/W	0.9928	likely_pathogenic	0.9964	pathogenic	-1.722	Destabilizing	0.982	D	0.759	deleterious	None	None	None	None	I
I/Y	0.9564	likely_pathogenic	0.9707	pathogenic	-1.498	Destabilizing	0.826	D	0.771	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.