TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16545	49858;49859;49860	chr2:178613176;178613175;178613174	chr2:179477903;179477902;179477901
N2AB	14904	44935;44936;44937	chr2:178613176;178613175;178613174	chr2:179477903;179477902;179477901
N2A	13977	42154;42155;42156	chr2:178613176;178613175;178613174	chr2:179477903;179477902;179477901
N2B	7480	22663;22664;22665	chr2:178613176;178613175;178613174	chr2:179477903;179477902;179477901
Novex-1	7605	23038;23039;23040	chr2:178613176;178613175;178613174	chr2:179477903;179477902;179477901
Novex-2	7672	23239;23240;23241	chr2:178613176;178613175;178613174	chr2:179477903;179477902;179477901
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: Fn3-7
• Domain position: 96
• Structural Position: 130
• Q(SASA): 0.0397
• 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
I/V	None	None	None	N	0.114	0.074	0.346992582518	gnomAD-4.0.0	1.20038E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31256E-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
I/A	0.8921	likely_pathogenic	0.8491	pathogenic	-3.168	Highly Destabilizing	0.115	N	0.632	neutral	None	None	None	None	N
I/C	0.9161	likely_pathogenic	0.8564	pathogenic	-2.408	Highly Destabilizing	0.944	D	0.717	prob.delet.	None	None	None	None	N
I/D	0.9994	likely_pathogenic	0.9992	pathogenic	-3.549	Highly Destabilizing	0.817	D	0.822	deleterious	None	None	None	None	N
I/E	0.9974	likely_pathogenic	0.9975	pathogenic	-3.265	Highly Destabilizing	0.817	D	0.767	deleterious	None	None	None	None	N
I/F	0.8783	likely_pathogenic	0.8527	pathogenic	-1.813	Destabilizing	0.687	D	0.703	prob.delet.	None	None	None	None	N
I/G	0.994	likely_pathogenic	0.9909	pathogenic	-3.717	Highly Destabilizing	0.817	D	0.721	deleterious	None	None	None	None	N
I/H	0.9976	likely_pathogenic	0.9972	pathogenic	-3.093	Highly Destabilizing	0.981	D	0.821	deleterious	None	None	None	None	N
I/K	0.9962	likely_pathogenic	0.9964	pathogenic	-2.304	Highly Destabilizing	0.771	D	0.769	deleterious	N	0.470731811	None	None	N
I/L	0.4157	ambiguous	0.3757	ambiguous	-1.518	Destabilizing	0.041	N	0.337	neutral	N	0.457400611	None	None	N
I/M	0.4499	ambiguous	0.3872	ambiguous	-1.759	Destabilizing	0.624	D	0.677	prob.neutral	N	0.472816655	None	None	N
I/N	0.9837	likely_pathogenic	0.9798	pathogenic	-2.859	Highly Destabilizing	0.931	D	0.812	deleterious	None	None	None	None	N
I/P	0.9763	likely_pathogenic	0.9664	pathogenic	-2.059	Highly Destabilizing	0.931	D	0.826	deleterious	None	None	None	None	N
I/Q	0.9926	likely_pathogenic	0.9921	pathogenic	-2.599	Highly Destabilizing	0.931	D	0.819	deleterious	None	None	None	None	N
I/R	0.9923	likely_pathogenic	0.9921	pathogenic	-2.142	Highly Destabilizing	0.771	D	0.81	deleterious	N	0.498936957	None	None	N
I/S	0.9653	likely_pathogenic	0.9527	pathogenic	-3.465	Highly Destabilizing	0.687	D	0.707	prob.delet.	None	None	None	None	N
I/T	0.9333	likely_pathogenic	0.9167	pathogenic	-3.036	Highly Destabilizing	0.321	N	0.683	prob.neutral	N	0.436733925	None	None	N
I/V	0.1448	likely_benign	0.1205	benign	-2.059	Highly Destabilizing	None	N	0.114	neutral	N	0.405536372	None	None	N
I/W	0.9979	likely_pathogenic	0.9978	pathogenic	-2.12	Highly Destabilizing	0.981	D	0.805	deleterious	None	None	None	None	N
I/Y	0.9935	likely_pathogenic	0.9924	pathogenic	-2.006	Highly Destabilizing	0.817	D	0.766	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.