TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4985	15178;15179;15180	chr2:178734971;178734970;178734969	chr2:179599698;179599697;179599696
N2AB	4668	14227;14228;14229	chr2:178734971;178734970;178734969	chr2:179599698;179599697;179599696
N2A	3741	11446;11447;11448	chr2:178734971;178734970;178734969	chr2:179599698;179599697;179599696
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-33
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.5449
• 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/T	rs750177841	-0.205	0.989	N	0.441	0.224	0.282575091529	gnomAD-2.1.1	5.67E-05	None	None	None	None	N	None	0	0	None	0	0	None	4.50586E-04	None	0	0	0
K/T	rs750177841	-0.205	0.989	N	0.441	0.224	0.282575091529	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	4.14422E-04	0
K/T	rs750177841	-0.205	0.989	N	0.441	0.224	0.282575091529	gnomAD-4.0.0	2.45542E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.31504E-04	1.62543E-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	0.761	likely_pathogenic	0.8353	pathogenic	-0.499	Destabilizing	0.996	D	0.443	neutral	None	None	None	None	N
K/C	0.9107	likely_pathogenic	0.9293	pathogenic	-0.402	Destabilizing	1.0	D	0.628	neutral	None	None	None	None	N
K/D	0.8886	likely_pathogenic	0.9267	pathogenic	-0.093	Destabilizing	0.995	D	0.444	neutral	None	None	None	None	N
K/E	0.4319	ambiguous	0.515	ambiguous	0.029	Stabilizing	0.989	D	0.431	neutral	N	0.453239198	None	None	N
K/F	0.9551	likely_pathogenic	0.9646	pathogenic	-0.067	Destabilizing	1.0	D	0.593	neutral	None	None	None	None	N
K/G	0.7755	likely_pathogenic	0.843	pathogenic	-0.877	Destabilizing	0.992	D	0.437	neutral	None	None	None	None	N
K/H	0.5607	ambiguous	0.6379	pathogenic	-1.153	Destabilizing	0.999	D	0.495	neutral	None	None	None	None	N
K/I	0.7796	likely_pathogenic	0.8163	pathogenic	0.486	Stabilizing	1.0	D	0.597	neutral	None	None	None	None	N
K/L	0.7065	likely_pathogenic	0.7444	pathogenic	0.486	Stabilizing	0.999	D	0.45	neutral	None	None	None	None	N
K/M	0.5703	likely_pathogenic	0.6146	pathogenic	0.266	Stabilizing	1.0	D	0.489	neutral	N	0.478960355	None	None	N
K/N	0.8032	likely_pathogenic	0.8585	pathogenic	-0.417	Destabilizing	0.733	D	0.254	neutral	N	0.443790687	None	None	N
K/P	0.962	likely_pathogenic	0.9764	pathogenic	0.188	Stabilizing	1.0	D	0.498	neutral	None	None	None	None	N
K/Q	0.221	likely_benign	0.2796	benign	-0.41	Destabilizing	0.998	D	0.457	neutral	N	0.449747832	None	None	N
K/R	0.0989	likely_benign	0.1065	benign	-0.627	Destabilizing	0.543	D	0.262	neutral	N	0.452760023	None	None	N
K/S	0.7708	likely_pathogenic	0.8354	pathogenic	-1.009	Destabilizing	0.992	D	0.425	neutral	None	None	None	None	N
K/T	0.5253	ambiguous	0.6144	pathogenic	-0.679	Destabilizing	0.989	D	0.441	neutral	N	0.448198013	None	None	N
K/V	0.7122	likely_pathogenic	0.7597	pathogenic	0.188	Stabilizing	0.999	D	0.548	neutral	None	None	None	None	N
K/W	0.9018	likely_pathogenic	0.9197	pathogenic	0.009	Stabilizing	1.0	D	0.652	neutral	None	None	None	None	N
K/Y	0.8871	likely_pathogenic	0.9079	pathogenic	0.266	Stabilizing	1.0	D	0.543	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.