TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9255	27988;27989;27990	chr2:178712067;178712066;178712065	chr2:179576794;179576793;179576792
N2AB	8938	27037;27038;27039	chr2:178712067;178712066;178712065	chr2:179576794;179576793;179576792
N2A	8011	24256;24257;24258	chr2:178712067;178712066;178712065	chr2:179576794;179576793;179576792
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-78
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.2574
• 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/V	rs2076737035	None	0.989	N	0.694	0.446	0.798820475059	gnomAD-4.0.0	2.05263E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69843E-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
F/A	0.9115	likely_pathogenic	0.9505	pathogenic	-2.099	Highly Destabilizing	0.996	D	0.736	prob.delet.	None	None	None	None	N
F/C	0.6935	likely_pathogenic	0.8127	pathogenic	-0.997	Destabilizing	1.0	D	0.807	deleterious	N	0.503405418	None	None	N
F/D	0.968	likely_pathogenic	0.9795	pathogenic	-0.738	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
F/E	0.9691	likely_pathogenic	0.9823	pathogenic	-0.669	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
F/G	0.9556	likely_pathogenic	0.9757	pathogenic	-2.426	Highly Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
F/H	0.8014	likely_pathogenic	0.8584	pathogenic	-0.747	Destabilizing	0.999	D	0.782	deleterious	None	None	None	None	N
F/I	0.4352	ambiguous	0.5457	ambiguous	-1.131	Destabilizing	0.998	D	0.715	prob.delet.	N	0.487497826	None	None	N
F/K	0.9545	likely_pathogenic	0.9685	pathogenic	-1.136	Destabilizing	0.999	D	0.824	deleterious	None	None	None	None	N
F/L	0.8886	likely_pathogenic	0.9209	pathogenic	-1.131	Destabilizing	0.989	D	0.63	neutral	N	0.504024716	None	None	N
F/M	0.7364	likely_pathogenic	0.7856	pathogenic	-0.802	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
F/N	0.8979	likely_pathogenic	0.9252	pathogenic	-1.138	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
F/P	0.9965	likely_pathogenic	0.9976	pathogenic	-1.445	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
F/Q	0.9231	likely_pathogenic	0.9525	pathogenic	-1.22	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
F/R	0.9056	likely_pathogenic	0.9338	pathogenic	-0.479	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
F/S	0.8058	likely_pathogenic	0.8814	pathogenic	-1.922	Destabilizing	0.998	D	0.787	deleterious	N	0.485457598	None	None	N
F/T	0.8483	likely_pathogenic	0.8982	pathogenic	-1.758	Destabilizing	0.999	D	0.802	deleterious	None	None	None	None	N
F/V	0.4734	ambiguous	0.588	pathogenic	-1.445	Destabilizing	0.989	D	0.694	prob.neutral	N	0.501117697	None	None	N
F/W	0.7142	likely_pathogenic	0.771	pathogenic	-0.421	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
F/Y	0.2677	likely_benign	0.2885	benign	-0.61	Destabilizing	0.333	N	0.331	neutral	N	0.484918881	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.