TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27542	82849;82850;82851	chr2:178563508;178563507;178563506	chr2:179428235;179428234;179428233
N2AB	25901	77926;77927;77928	chr2:178563508;178563507;178563506	chr2:179428235;179428234;179428233
N2A	24974	75145;75146;75147	chr2:178563508;178563507;178563506	chr2:179428235;179428234;179428233
N2B	18477	55654;55655;55656	chr2:178563508;178563507;178563506	chr2:179428235;179428234;179428233
Novex-1	18602	56029;56030;56031	chr2:178563508;178563507;178563506	chr2:179428235;179428234;179428233
Novex-2	18669	56230;56231;56232	chr2:178563508;178563507;178563506	chr2:179428235;179428234;179428233
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Fn3-88
• Domain position: 74
• Structural Position: 106
• Q(SASA): 0.1448
• 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/I	rs1704452293	None	0.565	N	0.731	0.472	0.504480301252	gnomAD-4.0.0	2.05262E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9947E-07	0	3.31334E-05

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	0.9977	likely_pathogenic	0.998	pathogenic	-2.901	Highly Destabilizing	0.775	D	0.833	deleterious	None	None	None	None	N
F/C	0.9705	likely_pathogenic	0.9721	pathogenic	-1.526	Destabilizing	0.995	D	0.834	deleterious	D	0.548619013	None	None	N
F/D	0.9989	likely_pathogenic	0.9993	pathogenic	-3.772	Highly Destabilizing	0.987	D	0.857	deleterious	None	None	None	None	N
F/E	0.9994	likely_pathogenic	0.9996	pathogenic	-3.529	Highly Destabilizing	0.961	D	0.859	deleterious	None	None	None	None	N
F/G	0.9967	likely_pathogenic	0.9977	pathogenic	-3.358	Highly Destabilizing	0.961	D	0.837	deleterious	None	None	None	None	N
F/H	0.9886	likely_pathogenic	0.9917	pathogenic	-2.311	Highly Destabilizing	0.923	D	0.788	deleterious	None	None	None	None	N
F/I	0.9605	likely_pathogenic	0.9468	pathogenic	-1.378	Destabilizing	0.565	D	0.731	prob.delet.	N	0.506010813	None	None	N
F/K	0.9994	likely_pathogenic	0.9995	pathogenic	-2.339	Highly Destabilizing	0.923	D	0.861	deleterious	None	None	None	None	N
F/L	0.9938	likely_pathogenic	0.992	pathogenic	-1.378	Destabilizing	0.008	N	0.354	neutral	N	0.505632419	None	None	N
F/M	0.9781	likely_pathogenic	0.9736	pathogenic	-0.987	Destabilizing	0.923	D	0.697	prob.neutral	None	None	None	None	N
F/N	0.9947	likely_pathogenic	0.9963	pathogenic	-3.047	Highly Destabilizing	0.961	D	0.865	deleterious	None	None	None	None	N
F/P	0.9999	likely_pathogenic	0.9999	pathogenic	-1.903	Destabilizing	0.987	D	0.877	deleterious	None	None	None	None	N
F/Q	0.9991	likely_pathogenic	0.9993	pathogenic	-2.87	Highly Destabilizing	0.961	D	0.869	deleterious	None	None	None	None	N
F/R	0.9985	likely_pathogenic	0.9988	pathogenic	-2.1	Highly Destabilizing	0.961	D	0.867	deleterious	None	None	None	None	N
F/S	0.9964	likely_pathogenic	0.9975	pathogenic	-3.465	Highly Destabilizing	0.901	D	0.832	deleterious	D	0.548619013	None	None	N
F/T	0.9981	likely_pathogenic	0.9984	pathogenic	-3.1	Highly Destabilizing	0.923	D	0.837	deleterious	None	None	None	None	N
F/V	0.9659	likely_pathogenic	0.9604	pathogenic	-1.903	Destabilizing	0.565	D	0.803	deleterious	N	0.473077078	None	None	N
F/W	0.8608	likely_pathogenic	0.8795	pathogenic	-0.645	Destabilizing	0.989	D	0.717	prob.delet.	None	None	None	None	N
F/Y	0.222	likely_benign	0.2849	benign	-1.083	Destabilizing	0.008	N	0.287	neutral	N	0.489088781	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.