TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21003	63232;63233;63234	chr2:178588718;178588717;178588716	chr2:179453445;179453444;179453443
N2AB	19362	58309;58310;58311	chr2:178588718;178588717;178588716	chr2:179453445;179453444;179453443
N2A	18435	55528;55529;55530	chr2:178588718;178588717;178588716	chr2:179453445;179453444;179453443
N2B	11938	36037;36038;36039	chr2:178588718;178588717;178588716	chr2:179453445;179453444;179453443
Novex-1	12063	36412;36413;36414	chr2:178588718;178588717;178588716	chr2:179453445;179453444;179453443
Novex-2	12130	36613;36614;36615	chr2:178588718;178588717;178588716	chr2:179453445;179453444;179453443
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: Fn3-40
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.2183
• 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	rs794729472	None	1.0	N	0.741	0.28	0.215869574891	gnomAD-4.0.0	7.52863E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.89611E-06	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	0.9442	likely_pathogenic	0.9416	pathogenic	-1.479	Destabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	N
K/C	0.8741	likely_pathogenic	0.8946	pathogenic	-1.591	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
K/D	0.9941	likely_pathogenic	0.9937	pathogenic	-1.546	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
K/E	0.8904	likely_pathogenic	0.8942	pathogenic	-1.289	Destabilizing	0.999	D	0.612	neutral	N	0.520212385	None	None	N
K/F	0.9674	likely_pathogenic	0.9759	pathogenic	-0.892	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
K/G	0.9632	likely_pathogenic	0.9585	pathogenic	-1.928	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
K/H	0.6599	likely_pathogenic	0.6794	pathogenic	-2.048	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
K/I	0.9225	likely_pathogenic	0.9272	pathogenic	-0.228	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
K/L	0.8191	likely_pathogenic	0.8408	pathogenic	-0.228	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
K/M	0.6305	likely_pathogenic	0.6674	pathogenic	-0.527	Destabilizing	1.0	D	0.799	deleterious	N	0.478614168	None	None	N
K/N	0.9718	likely_pathogenic	0.9736	pathogenic	-1.539	Destabilizing	1.0	D	0.741	deleterious	N	0.4756252	None	None	N
K/P	0.9982	likely_pathogenic	0.9981	pathogenic	-0.623	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
K/Q	0.453	ambiguous	0.4537	ambiguous	-1.331	Destabilizing	1.0	D	0.717	prob.delet.	N	0.499317038	None	None	N
K/R	0.0857	likely_benign	0.0889	benign	-0.99	Destabilizing	0.999	D	0.57	neutral	N	0.394824446	None	None	N
K/S	0.9788	likely_pathogenic	0.9798	pathogenic	-2.165	Highly Destabilizing	0.999	D	0.671	neutral	None	None	None	None	N
K/T	0.921	likely_pathogenic	0.918	pathogenic	-1.66	Destabilizing	1.0	D	0.809	deleterious	N	0.479486314	None	None	N
K/V	0.8934	likely_pathogenic	0.8981	pathogenic	-0.623	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
K/W	0.9486	likely_pathogenic	0.9596	pathogenic	-0.869	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
K/Y	0.8967	likely_pathogenic	0.9152	pathogenic	-0.512	Destabilizing	1.0	D	0.881	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.