TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27409	82450;82451;82452	chr2:178563907;178563906;178563905	chr2:179428634;179428633;179428632
N2AB	25768	77527;77528;77529	chr2:178563907;178563906;178563905	chr2:179428634;179428633;179428632
N2A	24841	74746;74747;74748	chr2:178563907;178563906;178563905	chr2:179428634;179428633;179428632
N2B	18344	55255;55256;55257	chr2:178563907;178563906;178563905	chr2:179428634;179428633;179428632
Novex-1	18469	55630;55631;55632	chr2:178563907;178563906;178563905	chr2:179428634;179428633;179428632
Novex-2	18536	55831;55832;55833	chr2:178563907;178563906;178563905	chr2:179428634;179428633;179428632
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-87
• Domain position: 41
• Structural Position: 42
• Q(SASA): 0.2348
• 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
K/E	None	None	0.958	N	0.681	0.473	0.327952845175	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	3.66327E-05
K/N	rs1372169120	-2.179	0.988	N	0.806	0.43	0.294561560033	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
K/N	rs1372169120	-2.179	0.988	N	0.806	0.43	0.294561560033	gnomAD-4.0.0	1.59139E-06	None	None	None	None	N	None	0	2.28666E-05	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
K/A	0.9856	likely_pathogenic	0.9862	pathogenic	-1.584	Destabilizing	0.968	D	0.681	prob.neutral	None	None	None	None	N
K/C	0.9609	likely_pathogenic	0.9607	pathogenic	-1.561	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
K/D	0.9978	likely_pathogenic	0.9978	pathogenic	-2.19	Highly Destabilizing	0.995	D	0.821	deleterious	None	None	None	None	N
K/E	0.9707	likely_pathogenic	0.9722	pathogenic	-1.847	Destabilizing	0.958	D	0.681	prob.neutral	N	0.500348819	None	None	N
K/F	0.9941	likely_pathogenic	0.9952	pathogenic	-0.792	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
K/G	0.9855	likely_pathogenic	0.9859	pathogenic	-2.094	Highly Destabilizing	0.991	D	0.773	deleterious	None	None	None	None	N
K/H	0.8872	likely_pathogenic	0.8933	pathogenic	-1.768	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
K/I	0.9695	likely_pathogenic	0.9707	pathogenic	-0.11	Destabilizing	0.995	D	0.855	deleterious	None	None	None	None	N
K/L	0.9458	likely_pathogenic	0.9436	pathogenic	-0.11	Destabilizing	0.991	D	0.773	deleterious	None	None	None	None	N
K/M	0.8725	likely_pathogenic	0.8768	pathogenic	-0.476	Destabilizing	0.999	D	0.824	deleterious	D	0.523175332	None	None	N
K/N	0.9903	likely_pathogenic	0.9902	pathogenic	-2.024	Highly Destabilizing	0.988	D	0.806	deleterious	N	0.500348819	None	None	N
K/P	0.9994	likely_pathogenic	0.9994	pathogenic	-0.584	Destabilizing	0.998	D	0.833	deleterious	None	None	None	None	N
K/Q	0.751	likely_pathogenic	0.7694	pathogenic	-1.585	Destabilizing	0.988	D	0.807	deleterious	N	0.482244564	None	None	N
K/R	0.1404	likely_benign	0.1499	benign	-0.912	Destabilizing	0.142	N	0.38	neutral	N	0.439423372	None	None	N
K/S	0.9895	likely_pathogenic	0.9905	pathogenic	-2.558	Highly Destabilizing	0.968	D	0.721	prob.delet.	None	None	None	None	N
K/T	0.9653	likely_pathogenic	0.9653	pathogenic	-1.936	Destabilizing	0.988	D	0.785	deleterious	N	0.471760405	None	None	N
K/V	0.958	likely_pathogenic	0.9591	pathogenic	-0.584	Destabilizing	0.995	D	0.816	deleterious	None	None	None	None	N
K/W	0.9845	likely_pathogenic	0.9881	pathogenic	-0.82	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
K/Y	0.9637	likely_pathogenic	0.9716	pathogenic	-0.492	Destabilizing	0.998	D	0.855	deleterious	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.