TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5927	18004;18005;18006	chr2:178730754;178730753;178730752	chr2:179595481;179595480;179595479
N2AB	5610	17053;17054;17055	chr2:178730754;178730753;178730752	chr2:179595481;179595480;179595479
N2A	4683	14272;14273;14274	chr2:178730754;178730753;178730752	chr2:179595481;179595480;179595479
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-43
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.7696
• 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/Q	None	None	0.31	N	0.167	0.108	0.115124310173	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.2874	likely_benign	0.2976	benign	-0.032	Destabilizing	0.863	D	0.353	neutral	None	None	None	None	N
K/C	0.7883	likely_pathogenic	0.782	pathogenic	0.024	Stabilizing	0.999	D	0.437	neutral	None	None	None	None	N
K/D	0.3571	ambiguous	0.3991	ambiguous	0.023	Stabilizing	0.884	D	0.37	neutral	None	None	None	None	N
K/E	0.1412	likely_benign	0.1582	benign	0.053	Stabilizing	0.134	N	0.177	neutral	N	0.3996804	None	None	N
K/F	0.8018	likely_pathogenic	0.8112	pathogenic	-0.051	Destabilizing	0.997	D	0.439	neutral	None	None	None	None	N
K/G	0.3927	ambiguous	0.4118	ambiguous	-0.291	Destabilizing	0.969	D	0.453	neutral	None	None	None	None	N
K/H	0.328	likely_benign	0.3225	benign	-0.658	Destabilizing	0.991	D	0.405	neutral	None	None	None	None	N
K/I	0.3976	ambiguous	0.4267	ambiguous	0.59	Stabilizing	0.996	D	0.447	neutral	N	0.493110637	None	None	N
K/L	0.3938	ambiguous	0.4058	ambiguous	0.59	Stabilizing	0.939	D	0.464	neutral	None	None	None	None	N
K/M	0.2338	likely_benign	0.2424	benign	0.403	Stabilizing	0.997	D	0.402	neutral	None	None	None	None	N
K/N	0.2544	likely_benign	0.2809	benign	0.29	Stabilizing	0.959	D	0.39	neutral	N	0.386441744	None	None	N
K/P	0.3514	ambiguous	0.3771	ambiguous	0.412	Stabilizing	0.046	N	0.215	neutral	None	None	None	None	N
K/Q	0.123	likely_benign	0.1226	benign	0.135	Stabilizing	0.31	N	0.167	neutral	N	0.45001322	None	None	N
K/R	0.0962	likely_benign	0.0942	benign	-0.125	Destabilizing	0.92	D	0.388	neutral	N	0.446972915	None	None	N
K/S	0.3176	likely_benign	0.3386	benign	-0.187	Destabilizing	0.939	D	0.329	neutral	None	None	None	None	N
K/T	0.1537	likely_benign	0.1667	benign	0.003	Stabilizing	0.959	D	0.423	neutral	N	0.433080898	None	None	N
K/V	0.3396	likely_benign	0.362	ambiguous	0.412	Stabilizing	0.969	D	0.455	neutral	None	None	None	None	N
K/W	0.8199	likely_pathogenic	0.8184	pathogenic	-0.043	Destabilizing	0.999	D	0.515	neutral	None	None	None	None	N
K/Y	0.6387	likely_pathogenic	0.6426	pathogenic	0.276	Stabilizing	0.997	D	0.427	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.