TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9946	30061;30062;30063	chr2:178704636;178704635;178704634	chr2:179569363;179569362;179569361
N2AB	9629	29110;29111;29112	chr2:178704636;178704635;178704634	chr2:179569363;179569362;179569361
N2A	8702	26329;26330;26331	chr2:178704636;178704635;178704634	chr2:179569363;179569362;179569361
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-84
• Domain position: 47
• Structural Position: 115
• Q(SASA): 0.0815
• 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	rs1181662412	-0.464	0.993	None	0.686	0.287	0.119812018005	gnomAD-2.1.1	8.13E-06	None	None	None	None	N	None	0	0	None	0	1.126E-04	None	0	None	0	0	0
K/N	rs1181662412	-0.464	0.993	None	0.686	0.287	0.119812018005	gnomAD-4.0.0	1.59444E-06	None	None	None	None	N	None	0	0	None	0	2.77331E-05	None	0	0	0	0	0
K/T	rs1268571982	-0.684	0.993	None	0.684	0.414	0.330589388543	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	0	None	0	5.63E-05	None	0	None	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
K/A	0.8516	likely_pathogenic	0.9183	pathogenic	-0.537	Destabilizing	0.983	D	0.499	neutral	None	None	None	None	N
K/C	0.9463	likely_pathogenic	0.9685	pathogenic	-0.433	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
K/D	0.8887	likely_pathogenic	0.9435	pathogenic	0.044	Stabilizing	0.995	D	0.675	prob.neutral	None	None	None	None	N
K/E	0.7142	likely_pathogenic	0.8299	pathogenic	0.149	Stabilizing	0.955	D	0.398	neutral	None	None	None	None	N
K/F	0.9742	likely_pathogenic	0.9866	pathogenic	-0.293	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
K/G	0.9169	likely_pathogenic	0.9604	pathogenic	-0.889	Destabilizing	0.995	D	0.64	neutral	None	None	None	None	N
K/H	0.6389	likely_pathogenic	0.7138	pathogenic	-1.216	Destabilizing	0.999	D	0.684	prob.neutral	None	None	None	None	N
K/I	0.7681	likely_pathogenic	0.8609	pathogenic	0.366	Stabilizing	0.997	D	0.72	prob.delet.	None	None	None	None	N
K/L	0.7868	likely_pathogenic	0.862	pathogenic	0.366	Stabilizing	0.995	D	0.64	neutral	None	None	None	None	N
K/M	0.6944	likely_pathogenic	0.8004	pathogenic	0.236	Stabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
K/N	0.7959	likely_pathogenic	0.8819	pathogenic	-0.293	Destabilizing	0.993	D	0.686	prob.neutral	None	None	None	None	N
K/P	0.9807	likely_pathogenic	0.9857	pathogenic	0.095	Stabilizing	0.998	D	0.7	prob.neutral	None	None	None	None	N
K/Q	0.4926	ambiguous	0.6139	pathogenic	-0.336	Destabilizing	0.568	D	0.249	neutral	None	None	None	None	N
K/R	0.1462	likely_benign	0.1746	benign	-0.486	Destabilizing	0.955	D	0.484	neutral	None	None	None	None	N
K/S	0.8763	likely_pathogenic	0.9343	pathogenic	-0.942	Destabilizing	0.983	D	0.514	neutral	None	None	None	None	N
K/T	0.5363	ambiguous	0.6632	pathogenic	-0.627	Destabilizing	0.993	D	0.684	prob.neutral	None	None	None	None	N
K/V	0.7713	likely_pathogenic	0.8574	pathogenic	0.095	Stabilizing	0.998	D	0.673	neutral	None	None	None	None	N
K/W	0.9739	likely_pathogenic	0.9858	pathogenic	-0.189	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
K/Y	0.909	likely_pathogenic	0.9457	pathogenic	0.099	Stabilizing	0.999	D	0.681	prob.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.