TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5857	17794;17795;17796	chr2:178731096;178731095;178731094	chr2:179595823;179595822;179595821
N2AB	5540	16843;16844;16845	chr2:178731096;178731095;178731094	chr2:179595823;179595822;179595821
N2A	4613	14062;14063;14064	chr2:178731096;178731095;178731094	chr2:179595823;179595822;179595821
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-42
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.1365
• 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
F/L	rs779004240	-2.004	None	N	0.199	0.179	0.227934060464	gnomAD-2.1.1	2.41E-05	None	None	None	None	N	None	0	1.73974E-04	None	0	0	None	0	None	0	0	0
F/L	rs779004240	-2.004	None	N	0.199	0.179	0.227934060464	gnomAD-4.0.0	1.11399E-05	None	None	None	None	N	None	0	1.60088E-04	None	0	0	None	0	0	0	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
F/A	0.7284	likely_pathogenic	0.7665	pathogenic	-2.634	Highly Destabilizing	0.129	N	0.515	neutral	None	None	None	None	N
F/C	0.3122	likely_benign	0.3832	ambiguous	-1.385	Destabilizing	0.978	D	0.561	neutral	N	0.484511246	None	None	N
F/D	0.8879	likely_pathogenic	0.92	pathogenic	-2.21	Highly Destabilizing	0.716	D	0.609	neutral	None	None	None	None	N
F/E	0.8347	likely_pathogenic	0.8771	pathogenic	-2.065	Highly Destabilizing	0.418	N	0.599	neutral	None	None	None	None	N
F/G	0.8388	likely_pathogenic	0.8695	pathogenic	-3.014	Highly Destabilizing	0.264	N	0.565	neutral	None	None	None	None	N
F/H	0.4281	ambiguous	0.4728	ambiguous	-1.275	Destabilizing	0.716	D	0.543	neutral	None	None	None	None	N
F/I	0.323	likely_benign	0.378	ambiguous	-1.431	Destabilizing	0.007	N	0.227	neutral	N	0.486667454	None	None	N
F/K	0.6832	likely_pathogenic	0.7579	pathogenic	-1.59	Destabilizing	0.418	N	0.595	neutral	None	None	None	None	N
F/L	0.7058	likely_pathogenic	0.7576	pathogenic	-1.431	Destabilizing	None	N	0.199	neutral	N	0.436641278	None	None	N
F/M	0.464	ambiguous	0.506	ambiguous	-1.087	Destabilizing	0.716	D	0.526	neutral	None	None	None	None	N
F/N	0.6058	likely_pathogenic	0.6902	pathogenic	-1.815	Destabilizing	0.716	D	0.607	neutral	None	None	None	None	N
F/P	0.9987	likely_pathogenic	0.9991	pathogenic	-1.835	Destabilizing	0.836	D	0.602	neutral	None	None	None	None	N
F/Q	0.6542	likely_pathogenic	0.6993	pathogenic	-1.886	Destabilizing	0.836	D	0.605	neutral	None	None	None	None	N
F/R	0.546	ambiguous	0.6252	pathogenic	-0.931	Destabilizing	0.716	D	0.605	neutral	None	None	None	None	N
F/S	0.4912	ambiguous	0.5694	pathogenic	-2.543	Highly Destabilizing	0.007	N	0.44	neutral	N	0.474989023	None	None	N
F/T	0.617	likely_pathogenic	0.6731	pathogenic	-2.305	Highly Destabilizing	0.264	N	0.519	neutral	None	None	None	None	N
F/V	0.3337	likely_benign	0.387	ambiguous	-1.835	Destabilizing	0.101	N	0.477	neutral	N	0.502290267	None	None	N
F/W	0.3512	ambiguous	0.3913	ambiguous	-0.353	Destabilizing	0.951	D	0.551	neutral	None	None	None	None	N
F/Y	0.0947	likely_benign	0.1052	benign	-0.65	Destabilizing	0.002	N	0.223	neutral	N	0.445452763	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.