TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5391	16396;16397;16398	chr2:178733005;178733004;178733003	chr2:179597732;179597731;179597730
N2AB	5074	15445;15446;15447	chr2:178733005;178733004;178733003	chr2:179597732;179597731;179597730
N2A	4147	12664;12665;12666	chr2:178733005;178733004;178733003	chr2:179597732;179597731;179597730
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-37
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.1781
• 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	rs1290194262	-1.664	0.006	N	0.323	0.249	0.409398589964	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14837E-04	0	None	0	0	None	0	None	0	0	0
F/L	rs1290194262	-1.664	0.006	N	0.323	0.249	0.409398589964	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
F/L	rs1290194262	-1.664	0.006	N	0.323	0.249	0.409398589964	gnomAD-4.0.0	6.84329E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99517E-07	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	0.8586	likely_pathogenic	0.8599	pathogenic	-2.448	Highly Destabilizing	0.707	D	0.599	neutral	None	None	None	None	N
F/C	0.5513	ambiguous	0.5428	ambiguous	-1.272	Destabilizing	0.993	D	0.717	prob.delet.	N	0.486650839	None	None	N
F/D	0.9356	likely_pathogenic	0.936	pathogenic	-1.321	Destabilizing	0.981	D	0.765	deleterious	None	None	None	None	N
F/E	0.9014	likely_pathogenic	0.9028	pathogenic	-1.232	Destabilizing	0.945	D	0.759	deleterious	None	None	None	None	N
F/G	0.9158	likely_pathogenic	0.916	pathogenic	-2.778	Highly Destabilizing	0.945	D	0.733	prob.delet.	None	None	None	None	N
F/H	0.5629	ambiguous	0.5549	ambiguous	-0.985	Destabilizing	0.995	D	0.682	prob.neutral	None	None	None	None	N
F/I	0.539	ambiguous	0.5254	ambiguous	-1.442	Destabilizing	0.477	N	0.497	neutral	N	0.488283607	None	None	N
F/K	0.9047	likely_pathogenic	0.9012	pathogenic	-1.145	Destabilizing	0.945	D	0.745	deleterious	None	None	None	None	N
F/L	0.8753	likely_pathogenic	0.8591	pathogenic	-1.442	Destabilizing	0.006	N	0.323	neutral	N	0.436641278	None	None	N
F/M	0.6689	likely_pathogenic	0.6532	pathogenic	-1.158	Destabilizing	0.894	D	0.647	neutral	None	None	None	None	N
F/N	0.7795	likely_pathogenic	0.7713	pathogenic	-1.138	Destabilizing	0.981	D	0.766	deleterious	None	None	None	None	N
F/P	0.9995	likely_pathogenic	0.9994	pathogenic	-1.774	Destabilizing	0.981	D	0.759	deleterious	None	None	None	None	N
F/Q	0.8026	likely_pathogenic	0.8011	pathogenic	-1.303	Destabilizing	0.981	D	0.757	deleterious	None	None	None	None	N
F/R	0.8039	likely_pathogenic	0.8	pathogenic	-0.433	Destabilizing	0.945	D	0.767	deleterious	None	None	None	None	N
F/S	0.6768	likely_pathogenic	0.6729	pathogenic	-1.978	Destabilizing	0.928	D	0.694	prob.neutral	N	0.445628908	None	None	N
F/T	0.8104	likely_pathogenic	0.8036	pathogenic	-1.801	Destabilizing	0.894	D	0.673	neutral	None	None	None	None	N
F/V	0.5428	ambiguous	0.5312	ambiguous	-1.774	Destabilizing	0.477	N	0.523	neutral	N	0.461999218	None	None	N
F/W	0.4827	ambiguous	0.462	ambiguous	-0.444	Destabilizing	0.995	D	0.636	neutral	None	None	None	None	N
F/Y	0.1249	likely_benign	0.1268	benign	-0.651	Destabilizing	0.787	D	0.521	neutral	N	0.418516877	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.