TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22297	67114;67115;67116	chr2:178580490;178580489;178580488	chr2:179445217;179445216;179445215
N2AB	20656	62191;62192;62193	chr2:178580490;178580489;178580488	chr2:179445217;179445216;179445215
N2A	19729	59410;59411;59412	chr2:178580490;178580489;178580488	chr2:179445217;179445216;179445215
N2B	13232	39919;39920;39921	chr2:178580490;178580489;178580488	chr2:179445217;179445216;179445215
Novex-1	13357	40294;40295;40296	chr2:178580490;178580489;178580488	chr2:179445217;179445216;179445215
Novex-2	13424	40495;40496;40497	chr2:178580490;178580489;178580488	chr2:179445217;179445216;179445215
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-126
• Domain position: 33
• Structural Position: 50
• Q(SASA): 0.1407
• 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	rs1013098448	None	1.0	D	0.739	0.436	0.180583059064	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/N	rs1013098448	None	1.0	D	0.739	0.436	0.180583059064	gnomAD-4.0.0	6.57583E-06	None	None	None	None	N	None	2.41336E-05	0	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	0.9914	likely_pathogenic	0.9906	pathogenic	-0.912	Destabilizing	0.999	D	0.646	neutral	None	None	None	None	N
K/C	0.9766	likely_pathogenic	0.9699	pathogenic	-0.865	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
K/D	0.9984	likely_pathogenic	0.9984	pathogenic	-0.172	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
K/E	0.9918	likely_pathogenic	0.9906	pathogenic	0.018	Stabilizing	0.999	D	0.557	neutral	D	0.526652147	None	None	N
K/F	0.9912	likely_pathogenic	0.9894	pathogenic	-0.329	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
K/G	0.9945	likely_pathogenic	0.9941	pathogenic	-1.343	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
K/H	0.8902	likely_pathogenic	0.8709	pathogenic	-1.439	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
K/I	0.9647	likely_pathogenic	0.9558	pathogenic	0.248	Stabilizing	1.0	D	0.843	deleterious	D	0.525384699	None	None	N
K/L	0.9367	likely_pathogenic	0.915	pathogenic	0.248	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
K/M	0.9264	likely_pathogenic	0.916	pathogenic	-0.009	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
K/N	0.9942	likely_pathogenic	0.994	pathogenic	-0.796	Destabilizing	1.0	D	0.739	prob.delet.	D	0.526398657	None	None	N
K/P	0.9972	likely_pathogenic	0.9971	pathogenic	-0.11	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
K/Q	0.914	likely_pathogenic	0.8936	pathogenic	-0.69	Destabilizing	1.0	D	0.727	prob.delet.	D	0.525891678	None	None	N
K/R	0.2174	likely_benign	0.1801	benign	-0.693	Destabilizing	0.999	D	0.579	neutral	N	0.462736914	None	None	N
K/S	0.9955	likely_pathogenic	0.995	pathogenic	-1.536	Destabilizing	0.999	D	0.607	neutral	None	None	None	None	N
K/T	0.9848	likely_pathogenic	0.9833	pathogenic	-1.103	Destabilizing	1.0	D	0.771	deleterious	D	0.526145168	None	None	N
K/V	0.955	likely_pathogenic	0.9444	pathogenic	-0.11	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
K/W	0.9949	likely_pathogenic	0.9924	pathogenic	-0.189	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
K/Y	0.9751	likely_pathogenic	0.9691	pathogenic	0.083	Stabilizing	1.0	D	0.823	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.