TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10012	30259;30260;30261	chr2:178704336;178704335;178704334	chr2:179569063;179569062;179569061
N2AB	9695	29308;29309;29310	chr2:178704336;178704335;178704334	chr2:179569063;179569062;179569061
N2A	8768	26527;26528;26529	chr2:178704336;178704335;178704334	chr2:179569063;179569062;179569061
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-85
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.078
• 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	None	None	0.925	None	0.68	0.27	0.502005994047	gnomAD-4.0.0	1.36827E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79878E-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	0.9951	likely_pathogenic	0.9942	pathogenic	-3.747	Highly Destabilizing	0.985	D	0.723	prob.delet.	None	None	None	None	N
F/C	0.9811	likely_pathogenic	0.9779	pathogenic	-2.256	Highly Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
F/D	0.999	likely_pathogenic	0.999	pathogenic	-3.883	Highly Destabilizing	0.999	D	0.848	deleterious	None	None	None	None	N
F/E	0.9992	likely_pathogenic	0.9991	pathogenic	-3.69	Highly Destabilizing	0.999	D	0.846	deleterious	None	None	None	None	N
F/G	0.9971	likely_pathogenic	0.9967	pathogenic	-4.118	Highly Destabilizing	0.999	D	0.834	deleterious	None	None	None	None	N
F/H	0.9925	likely_pathogenic	0.9925	pathogenic	-2.604	Highly Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
F/I	0.9182	likely_pathogenic	0.9068	pathogenic	-2.482	Highly Destabilizing	0.925	D	0.651	neutral	None	None	None	None	N
F/K	0.9988	likely_pathogenic	0.9987	pathogenic	-2.504	Highly Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
F/L	0.9867	likely_pathogenic	0.9852	pathogenic	-2.482	Highly Destabilizing	0.031	N	0.321	neutral	None	None	None	None	N
F/M	0.958	likely_pathogenic	0.9558	pathogenic	-2.189	Highly Destabilizing	0.991	D	0.74	deleterious	None	None	None	None	N
F/N	0.9962	likely_pathogenic	0.9959	pathogenic	-2.92	Highly Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
F/P	0.9998	likely_pathogenic	0.9998	pathogenic	-2.922	Highly Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
F/Q	0.9985	likely_pathogenic	0.9984	pathogenic	-2.914	Highly Destabilizing	0.999	D	0.851	deleterious	None	None	None	None	N
F/R	0.9971	likely_pathogenic	0.9969	pathogenic	-1.915	Destabilizing	0.999	D	0.846	deleterious	None	None	None	None	N
F/S	0.9962	likely_pathogenic	0.9956	pathogenic	-3.462	Highly Destabilizing	0.998	D	0.795	deleterious	None	None	None	None	N
F/T	0.996	likely_pathogenic	0.9958	pathogenic	-3.179	Highly Destabilizing	0.996	D	0.789	deleterious	None	None	None	None	N
F/V	0.9272	likely_pathogenic	0.9172	pathogenic	-2.922	Highly Destabilizing	0.925	D	0.68	prob.neutral	None	None	None	None	N
F/W	0.9496	likely_pathogenic	0.9468	pathogenic	-0.94	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
F/Y	0.6933	likely_pathogenic	0.6711	pathogenic	-1.583	Destabilizing	0.993	D	0.654	neutral	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.