TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24472	73639;73640;73641	chr2:178572718;178572717;178572716	chr2:179437445;179437444;179437443
N2AB	22831	68716;68717;68718	chr2:178572718;178572717;178572716	chr2:179437445;179437444;179437443
N2A	21904	65935;65936;65937	chr2:178572718;178572717;178572716	chr2:179437445;179437444;179437443
N2B	15407	46444;46445;46446	chr2:178572718;178572717;178572716	chr2:179437445;179437444;179437443
Novex-1	15532	46819;46820;46821	chr2:178572718;178572717;178572716	chr2:179437445;179437444;179437443
Novex-2	15599	47020;47021;47022	chr2:178572718;178572717;178572716	chr2:179437445;179437444;179437443
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-132
• Domain position: 42
• Structural Position: 73
• Q(SASA): 0.1754
• 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/N	rs1239070012	-0.713	0.896	N	0.453	0.112	0.166414681773	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	0	1.65948E-04
K/N	rs1239070012	-0.713	0.896	N	0.453	0.112	0.166414681773	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/N	rs1239070012	-0.713	0.896	N	0.453	0.112	0.166414681773	gnomAD-4.0.0	3.84493E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78822E-06	0	2.84527E-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
K/A	0.2622	likely_benign	0.2946	benign	-0.004	Destabilizing	0.919	D	0.393	neutral	None	None	None	None	N
K/C	0.6051	likely_pathogenic	0.6391	pathogenic	-0.12	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
K/D	0.4153	ambiguous	0.4488	ambiguous	0.11	Stabilizing	0.988	D	0.488	neutral	None	None	None	None	N
K/E	0.1678	likely_benign	0.1799	benign	0.115	Stabilizing	0.896	D	0.42	neutral	N	0.469081771	None	None	N
K/F	0.7298	likely_pathogenic	0.7521	pathogenic	-0.217	Destabilizing	0.996	D	0.589	neutral	None	None	None	None	N
K/G	0.2953	likely_benign	0.3156	benign	-0.212	Destabilizing	0.959	D	0.491	neutral	None	None	None	None	N
K/H	0.2355	likely_benign	0.2434	benign	-0.567	Destabilizing	0.988	D	0.484	neutral	None	None	None	None	N
K/I	0.3689	ambiguous	0.3933	ambiguous	0.465	Stabilizing	0.984	D	0.576	neutral	N	0.494209502	None	None	N
K/L	0.335	likely_benign	0.3587	ambiguous	0.465	Stabilizing	0.919	D	0.491	neutral	None	None	None	None	N
K/M	0.2581	likely_benign	0.2748	benign	0.333	Stabilizing	0.999	D	0.485	neutral	None	None	None	None	N
K/N	0.3315	likely_benign	0.3447	ambiguous	0.296	Stabilizing	0.896	D	0.453	neutral	N	0.452938882	None	None	N
K/P	0.6284	likely_pathogenic	0.6645	pathogenic	0.337	Stabilizing	0.996	D	0.487	neutral	None	None	None	None	N
K/Q	0.1287	likely_benign	0.1321	benign	0.095	Stabilizing	0.896	D	0.481	neutral	N	0.488283607	None	None	N
K/R	0.0655	likely_benign	0.0659	benign	-0.025	Destabilizing	0.011	N	0.168	neutral	N	0.332913904	None	None	N
K/S	0.3199	likely_benign	0.3434	ambiguous	-0.21	Destabilizing	0.919	D	0.415	neutral	None	None	None	None	N
K/T	0.1624	likely_benign	0.1726	benign	-0.055	Destabilizing	0.946	D	0.461	neutral	N	0.475277024	None	None	N
K/V	0.3211	likely_benign	0.3492	ambiguous	0.337	Stabilizing	0.988	D	0.5	neutral	None	None	None	None	N
K/W	0.6978	likely_pathogenic	0.7099	pathogenic	-0.214	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
K/Y	0.5524	ambiguous	0.5816	pathogenic	0.147	Stabilizing	0.996	D	0.529	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.