TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30829	92710;92711;92712	chr2:178549141;178549140;178549139	chr2:179413868;179413867;179413866
N2AB	29188	87787;87788;87789	chr2:178549141;178549140;178549139	chr2:179413868;179413867;179413866
N2A	28261	85006;85007;85008	chr2:178549141;178549140;178549139	chr2:179413868;179413867;179413866
N2B	21764	65515;65516;65517	chr2:178549141;178549140;178549139	chr2:179413868;179413867;179413866
Novex-1	21889	65890;65891;65892	chr2:178549141;178549140;178549139	chr2:179413868;179413867;179413866
Novex-2	21956	66091;66092;66093	chr2:178549141;178549140;178549139	chr2:179413868;179413867;179413866
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: Fn3-113
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.3874
• 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	rs764294218	-0.262	0.978	N	0.657	0.3	0.228597637076	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
K/N	rs764294218	-0.262	0.978	N	0.657	0.3	0.228597637076	gnomAD-4.0.0	4.77351E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.57373E-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	0.4379	ambiguous	0.4231	ambiguous	-0.456	Destabilizing	0.944	D	0.599	neutral	None	None	None	None	N
K/C	0.6335	likely_pathogenic	0.6247	pathogenic	-0.663	Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
K/D	0.7722	likely_pathogenic	0.7539	pathogenic	0.062	Stabilizing	0.992	D	0.807	deleterious	None	None	None	None	N
K/E	0.347	ambiguous	0.3052	benign	0.189	Stabilizing	0.928	D	0.477	neutral	N	0.506899158	None	None	N
K/F	0.7975	likely_pathogenic	0.7753	pathogenic	-0.101	Destabilizing	0.999	D	0.816	deleterious	None	None	None	None	N
K/G	0.6154	likely_pathogenic	0.5907	pathogenic	-0.819	Destabilizing	0.983	D	0.734	prob.delet.	None	None	None	None	N
K/H	0.2723	likely_benign	0.2499	benign	-0.989	Destabilizing	0.998	D	0.775	deleterious	None	None	None	None	N
K/I	0.4578	ambiguous	0.4405	ambiguous	0.48	Stabilizing	0.989	D	0.826	deleterious	N	0.478271773	None	None	N
K/L	0.4584	ambiguous	0.4345	ambiguous	0.48	Stabilizing	0.983	D	0.734	prob.delet.	None	None	None	None	N
K/M	0.2777	likely_benign	0.2708	benign	0.122	Stabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
K/N	0.5451	ambiguous	0.5121	ambiguous	-0.486	Destabilizing	0.978	D	0.657	neutral	N	0.471016844	None	None	N
K/P	0.9566	likely_pathogenic	0.9557	pathogenic	0.199	Stabilizing	0.997	D	0.817	deleterious	None	None	None	None	N
K/Q	0.1646	likely_benign	0.1489	benign	-0.474	Destabilizing	0.978	D	0.635	neutral	N	0.517518797	None	None	N
K/R	0.0767	likely_benign	0.0771	benign	-0.483	Destabilizing	0.085	N	0.331	neutral	N	0.452699314	None	None	N
K/S	0.4921	ambiguous	0.4659	ambiguous	-1.127	Destabilizing	0.944	D	0.567	neutral	None	None	None	None	N
K/T	0.1972	likely_benign	0.1938	benign	-0.788	Destabilizing	0.978	D	0.775	deleterious	N	0.504626857	None	None	N
K/V	0.3945	ambiguous	0.387	ambiguous	0.199	Stabilizing	0.992	D	0.805	deleterious	None	None	None	None	N
K/W	0.7712	likely_pathogenic	0.7474	pathogenic	-0.012	Destabilizing	0.999	D	0.81	deleterious	None	None	None	None	N
K/Y	0.6901	likely_pathogenic	0.6617	pathogenic	0.282	Stabilizing	0.997	D	0.823	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.