TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9461	28606;28607;28608	chr2:178710716;178710715;178710714	chr2:179575443;179575442;179575441
N2AB	9144	27655;27656;27657	chr2:178710716;178710715;178710714	chr2:179575443;179575442;179575441
N2A	8217	24874;24875;24876	chr2:178710716;178710715;178710714	chr2:179575443;179575442;179575441
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: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-80
• Domain position: 65
• Structural Position: 146
• Q(SASA): 0.6678
• 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	0.811	None	0.414	0.164	0.231873229951	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-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	0.3358	likely_benign	0.388	ambiguous	0.029	Stabilizing	0.919	D	0.41	neutral	None	None	None	None	N
K/C	0.85	likely_pathogenic	0.8954	pathogenic	-0.343	Destabilizing	0.999	D	0.493	neutral	None	None	None	None	N
K/D	0.571	likely_pathogenic	0.5824	pathogenic	0.023	Stabilizing	0.976	D	0.385	neutral	None	None	None	None	N
K/E	0.2156	likely_benign	0.1913	benign	0.034	Stabilizing	0.811	D	0.414	neutral	None	None	None	None	N
K/F	0.8345	likely_pathogenic	0.8762	pathogenic	-0.21	Destabilizing	0.996	D	0.448	neutral	None	None	None	None	N
K/G	0.4514	ambiguous	0.5121	ambiguous	-0.153	Destabilizing	0.919	D	0.423	neutral	None	None	None	None	N
K/H	0.4005	ambiguous	0.4626	ambiguous	-0.324	Destabilizing	0.997	D	0.391	neutral	None	None	None	None	N
K/I	0.5048	ambiguous	0.5178	ambiguous	0.426	Stabilizing	0.984	D	0.448	neutral	None	None	None	None	N
K/L	0.4675	ambiguous	0.5165	ambiguous	0.426	Stabilizing	0.919	D	0.41	neutral	None	None	None	None	N
K/M	0.365	ambiguous	0.3802	ambiguous	0.074	Stabilizing	0.997	D	0.391	neutral	None	None	None	None	N
K/N	0.4533	ambiguous	0.4683	ambiguous	0.109	Stabilizing	0.968	D	0.343	neutral	None	None	None	None	N
K/P	0.5655	likely_pathogenic	0.6354	pathogenic	0.32	Stabilizing	0.076	N	0.244	neutral	None	None	None	None	N
K/Q	0.1839	likely_benign	0.1944	benign	-0.014	Destabilizing	0.211	N	0.248	neutral	None	None	None	None	N
K/R	0.0902	likely_benign	0.0903	benign	-0.035	Destabilizing	0.026	N	0.261	neutral	None	None	None	None	N
K/S	0.4125	ambiguous	0.4591	ambiguous	-0.336	Destabilizing	0.919	D	0.389	neutral	None	None	None	None	N
K/T	0.2238	likely_benign	0.2461	benign	-0.18	Destabilizing	0.896	D	0.392	neutral	None	None	None	None	N
K/V	0.4568	ambiguous	0.4906	ambiguous	0.32	Stabilizing	0.988	D	0.389	neutral	None	None	None	None	N
K/W	0.8267	likely_pathogenic	0.8689	pathogenic	-0.272	Destabilizing	0.999	D	0.571	neutral	None	None	None	None	N
K/Y	0.7241	likely_pathogenic	0.7651	pathogenic	0.093	Stabilizing	0.996	D	0.438	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.