TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7145	21658;21659;21660	chr2:178723667;178723666;178723665	chr2:179588394;179588393;179588392
N2AB	6828	20707;20708;20709	chr2:178723667;178723666;178723665	chr2:179588394;179588393;179588392
N2A	5901	17926;17927;17928	chr2:178723667;178723666;178723665	chr2:179588394;179588393;179588392
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: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-56
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.4274
• 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
P/S	rs745988872	-0.68	0.058	N	0.239	0.046	0.137902524267	gnomAD-2.1.1	4.3E-06	None	None	None	None	N	None	0	3.14E-05	None	0	0	None	0	None	0	0	0
P/S	rs745988872	-0.68	0.058	N	0.239	0.046	0.137902524267	gnomAD-4.0.0	1.63743E-06	None	None	None	None	N	None	0	2.44475E-05	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
P/A	0.0644	likely_benign	0.0658	benign	-0.618	Destabilizing	0.698	D	0.451	neutral	N	0.467964263	None	None	N
P/C	0.4367	ambiguous	0.4603	ambiguous	-0.686	Destabilizing	0.998	D	0.673	neutral	None	None	None	None	N
P/D	0.2681	likely_benign	0.2796	benign	-0.264	Destabilizing	0.956	D	0.515	neutral	None	None	None	None	N
P/E	0.2106	likely_benign	0.2268	benign	-0.326	Destabilizing	0.956	D	0.507	neutral	None	None	None	None	N
P/F	0.3345	likely_benign	0.3373	benign	-0.563	Destabilizing	0.915	D	0.662	neutral	None	None	None	None	N
P/G	0.2432	likely_benign	0.2535	benign	-0.817	Destabilizing	0.754	D	0.501	neutral	None	None	None	None	N
P/H	0.1593	likely_benign	0.1678	benign	-0.268	Destabilizing	0.992	D	0.625	neutral	N	0.461870633	None	None	N
P/I	0.2467	likely_benign	0.2563	benign	-0.217	Destabilizing	0.978	D	0.661	neutral	None	None	None	None	N
P/K	0.2575	likely_benign	0.2703	benign	-0.575	Destabilizing	0.956	D	0.52	neutral	None	None	None	None	N
P/L	0.1075	likely_benign	0.1089	benign	-0.217	Destabilizing	0.942	D	0.591	neutral	N	0.463009495	None	None	N
P/M	0.251	likely_benign	0.257	benign	-0.401	Destabilizing	0.998	D	0.615	neutral	None	None	None	None	N
P/N	0.2231	likely_benign	0.2345	benign	-0.386	Destabilizing	0.956	D	0.613	neutral	None	None	None	None	N
P/Q	0.1413	likely_benign	0.1511	benign	-0.553	Destabilizing	0.956	D	0.578	neutral	None	None	None	None	N
P/R	0.1673	likely_benign	0.1773	benign	-0.099	Destabilizing	0.942	D	0.629	neutral	N	0.501538119	None	None	N
P/S	0.0962	likely_benign	0.0994	benign	-0.812	Destabilizing	0.058	N	0.239	neutral	N	0.443257819	None	None	N
P/T	0.0959	likely_benign	0.1007	benign	-0.763	Destabilizing	0.698	D	0.485	neutral	N	0.451373247	None	None	N
P/V	0.1754	likely_benign	0.1838	benign	-0.315	Destabilizing	0.956	D	0.542	neutral	None	None	None	None	N
P/W	0.5215	ambiguous	0.5332	ambiguous	-0.679	Destabilizing	0.998	D	0.7	prob.neutral	None	None	None	None	N
P/Y	0.3058	likely_benign	0.3116	benign	-0.38	Destabilizing	0.16	N	0.401	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.