TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22179	66760;66761;66762	chr2:178581733;178581732;178581731	chr2:179446460;179446459;179446458
N2AB	20538	61837;61838;61839	chr2:178581733;178581732;178581731	chr2:179446460;179446459;179446458
N2A	19611	59056;59057;59058	chr2:178581733;178581732;178581731	chr2:179446460;179446459;179446458
N2B	13114	39565;39566;39567	chr2:178581733;178581732;178581731	chr2:179446460;179446459;179446458
Novex-1	13239	39940;39941;39942	chr2:178581733;178581732;178581731	chr2:179446460;179446459;179446458
Novex-2	13306	40141;40142;40143	chr2:178581733;178581732;178581731	chr2:179446460;179446459;179446458
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: Fn3-49
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.7962
• Predicted PPI site: I

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	rs747865430	0.127	0.999	N	0.637	0.368	0.306695030598	gnomAD-2.1.1	8.33E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	9.24E-06	1.71292E-04
K/E	rs747865430	0.127	0.999	N	0.637	0.368	0.306695030598	gnomAD-4.0.0	3.20492E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87543E-06	0	3.04229E-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	0.6766	likely_pathogenic	0.7152	pathogenic	-0.306	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	I
K/C	0.8736	likely_pathogenic	0.8814	pathogenic	-0.629	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
K/D	0.9143	likely_pathogenic	0.9343	pathogenic	-0.269	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
K/E	0.5662	likely_pathogenic	0.6266	pathogenic	-0.196	Destabilizing	0.999	D	0.637	neutral	N	0.500317116	None	None	I
K/F	0.9236	likely_pathogenic	0.9293	pathogenic	-0.37	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
K/G	0.8586	likely_pathogenic	0.8901	pathogenic	-0.548	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
K/H	0.5776	likely_pathogenic	0.5991	pathogenic	-0.632	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	I
K/I	0.6335	likely_pathogenic	0.6649	pathogenic	0.279	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
K/L	0.6093	likely_pathogenic	0.6353	pathogenic	0.279	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
K/M	0.5075	ambiguous	0.5366	ambiguous	-0.212	Destabilizing	1.0	D	0.746	deleterious	N	0.474446658	None	None	I
K/N	0.8195	likely_pathogenic	0.8482	pathogenic	-0.297	Destabilizing	1.0	D	0.758	deleterious	N	0.479611218	None	None	I
K/P	0.5788	likely_pathogenic	0.6193	pathogenic	0.11	Stabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
K/Q	0.3006	likely_benign	0.3179	benign	-0.308	Destabilizing	1.0	D	0.745	deleterious	N	0.505128289	None	None	I
K/R	0.1098	likely_benign	0.1101	benign	-0.192	Destabilizing	0.999	D	0.62	neutral	N	0.460702722	None	None	I
K/S	0.7992	likely_pathogenic	0.831	pathogenic	-0.736	Destabilizing	0.999	D	0.678	prob.neutral	None	None	None	None	I
K/T	0.5387	ambiguous	0.5866	pathogenic	-0.488	Destabilizing	1.0	D	0.769	deleterious	N	0.520943104	None	None	I
K/V	0.6001	likely_pathogenic	0.6277	pathogenic	0.11	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
K/W	0.9379	likely_pathogenic	0.9461	pathogenic	-0.417	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
K/Y	0.8667	likely_pathogenic	0.8787	pathogenic	-0.086	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	I

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.