TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35183	105772;105773;105774	chr2:178531068;178531067;178531066	chr2:179395795;179395794;179395793
N2AB	33542	100849;100850;100851	chr2:178531068;178531067;178531066	chr2:179395795;179395794;179395793
N2A	32615	98068;98069;98070	chr2:178531068;178531067;178531066	chr2:179395795;179395794;179395793
N2B	26118	78577;78578;78579	chr2:178531068;178531067;178531066	chr2:179395795;179395794;179395793
Novex-1	26243	78952;78953;78954	chr2:178531068;178531067;178531066	chr2:179395795;179395794;179395793
Novex-2	26310	79153;79154;79155	chr2:178531068;178531067;178531066	chr2:179395795;179395794;179395793
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-164
• Domain position: 55
• Structural Position: 135
• Q(SASA): 0.5043
• 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	0.166	N	0.536	0.193	0.266843984389	gnomAD-4.0.0	1.32035E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.44375E-05	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	0.866	likely_pathogenic	0.868	pathogenic	-0.151	Destabilizing	0.209	N	0.618	neutral	None	None	None	None	N
K/C	0.928	likely_pathogenic	0.915	pathogenic	-0.476	Destabilizing	0.977	D	0.763	deleterious	None	None	None	None	N
K/D	0.9755	likely_pathogenic	0.9784	pathogenic	-0.726	Destabilizing	0.649	D	0.682	prob.neutral	None	None	None	None	N
K/E	0.7231	likely_pathogenic	0.7257	pathogenic	-0.724	Destabilizing	0.166	N	0.536	neutral	N	0.466775837	None	None	N
K/F	0.9704	likely_pathogenic	0.9706	pathogenic	-0.734	Destabilizing	0.649	D	0.765	deleterious	None	None	None	None	N
K/G	0.9332	likely_pathogenic	0.9398	pathogenic	-0.348	Destabilizing	0.345	N	0.683	prob.neutral	None	None	None	None	N
K/H	0.6253	likely_pathogenic	0.6164	pathogenic	-0.92	Destabilizing	0.004	N	0.463	neutral	None	None	None	None	N
K/I	0.8215	likely_pathogenic	0.8071	pathogenic	0.294	Stabilizing	0.739	D	0.767	deleterious	N	0.47735819	None	None	N
K/L	0.7953	likely_pathogenic	0.8088	pathogenic	0.294	Stabilizing	0.345	N	0.699	prob.neutral	None	None	None	None	N
K/M	0.6997	likely_pathogenic	0.685	pathogenic	0.525	Stabilizing	0.977	D	0.706	prob.neutral	None	None	None	None	N
K/N	0.9112	likely_pathogenic	0.9168	pathogenic	-0.139	Destabilizing	0.166	N	0.565	neutral	N	0.444843127	None	None	N
K/P	0.9896	likely_pathogenic	0.9931	pathogenic	0.173	Stabilizing	0.789	D	0.731	prob.delet.	None	None	None	None	N
K/Q	0.3768	ambiguous	0.3854	ambiguous	-0.536	Destabilizing	0.582	D	0.591	neutral	N	0.480649211	None	None	N
K/R	0.1341	likely_benign	0.1387	benign	0.005	Stabilizing	0.001	N	0.271	neutral	N	0.475203319	None	None	N
K/S	0.8811	likely_pathogenic	0.8881	pathogenic	-0.578	Destabilizing	0.02	N	0.279	neutral	None	None	None	None	N
K/T	0.6384	likely_pathogenic	0.6176	pathogenic	-0.436	Destabilizing	0.166	N	0.69	prob.neutral	N	0.472067013	None	None	N
K/V	0.8103	likely_pathogenic	0.7916	pathogenic	0.173	Stabilizing	0.789	D	0.699	prob.neutral	None	None	None	None	N
K/W	0.9637	likely_pathogenic	0.9658	pathogenic	-0.724	Destabilizing	0.977	D	0.765	deleterious	None	None	None	None	N
K/Y	0.9242	likely_pathogenic	0.9201	pathogenic	-0.234	Destabilizing	0.48	N	0.759	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.