TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9415	28468;28469;28470	chr2:178710854;178710853;178710852	chr2:179575581;179575580;179575579
N2AB	9098	27517;27518;27519	chr2:178710854;178710853;178710852	chr2:179575581;179575580;179575579
N2A	8171	24736;24737;24738	chr2:178710854;178710853;178710852	chr2:179575581;179575580;179575579
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: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-80
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.4896
• Predicted PPI site: I

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
D/E	rs2076551495	None	0.003	None	0.248	0.129	0.130388298395	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
D/E	rs2076551495	None	0.003	None	0.248	0.129	0.130388298395	gnomAD-4.0.0	1.59109E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85799E-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
D/A	0.1196	likely_benign	0.1494	benign	-0.371	Destabilizing	0.007	N	0.46	neutral	None	None	None	None	I
D/C	0.5374	ambiguous	0.5935	pathogenic	-0.086	Destabilizing	0.983	D	0.583	neutral	None	None	None	None	I
D/E	0.1472	likely_benign	0.1798	benign	-0.316	Destabilizing	0.003	N	0.248	neutral	None	None	None	None	I
D/F	0.4509	ambiguous	0.5177	ambiguous	0.013	Stabilizing	0.94	D	0.585	neutral	None	None	None	None	I
D/G	0.1535	likely_benign	0.1923	benign	-0.639	Destabilizing	0.001	N	0.337	neutral	None	None	None	None	I
D/H	0.16	likely_benign	0.2136	benign	0.091	Stabilizing	0.921	D	0.577	neutral	None	None	None	None	I
D/I	0.2187	likely_benign	0.2534	benign	0.309	Stabilizing	0.836	D	0.591	neutral	None	None	None	None	I
D/K	0.1951	likely_benign	0.2548	benign	0.267	Stabilizing	0.002	N	0.359	neutral	None	None	None	None	I
D/L	0.2493	likely_benign	0.3093	benign	0.309	Stabilizing	0.418	N	0.557	neutral	None	None	None	None	I
D/M	0.4661	ambiguous	0.5443	ambiguous	0.462	Stabilizing	0.983	D	0.577	neutral	None	None	None	None	I
D/N	0.0782	likely_benign	0.0966	benign	-0.292	Destabilizing	0.351	N	0.497	neutral	None	None	None	None	I
D/P	0.6646	likely_pathogenic	0.752	pathogenic	0.106	Stabilizing	0.593	D	0.578	neutral	None	None	None	None	I
D/Q	0.192	likely_benign	0.261	benign	-0.179	Destabilizing	0.418	N	0.515	neutral	None	None	None	None	I
D/R	0.1918	likely_benign	0.2643	benign	0.481	Stabilizing	0.264	N	0.569	neutral	None	None	None	None	I
D/S	0.0873	likely_benign	0.1097	benign	-0.402	Destabilizing	0.027	N	0.265	neutral	None	None	None	None	I
D/T	0.1493	likely_benign	0.1883	benign	-0.171	Destabilizing	0.418	N	0.487	neutral	None	None	None	None	I
D/V	0.13	likely_benign	0.1512	benign	0.106	Stabilizing	0.351	N	0.562	neutral	None	None	None	None	I
D/W	0.7925	likely_pathogenic	0.8482	pathogenic	0.244	Stabilizing	0.983	D	0.613	neutral	None	None	None	None	I
D/Y	0.1687	likely_benign	0.1988	benign	0.283	Stabilizing	0.921	D	0.583	neutral	None	None	None	None	I

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.