TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6255	18988;18989;18990	chr2:178729393;178729392;178729391	chr2:179594120;179594119;179594118
N2AB	5938	18037;18038;18039	chr2:178729393;178729392;178729391	chr2:179594120;179594119;179594118
N2A	5011	15256;15257;15258	chr2:178729393;178729392;178729391	chr2:179594120;179594119;179594118
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: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-46
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.1467
• 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
N/D	rs2079983036	None	0.007	N	0.399	0.079	0.139678290688	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07039E-04	0
N/D	rs2079983036	None	0.007	N	0.399	0.079	0.139678290688	gnomAD-4.0.0	2.5627E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.67996E-05	0
N/K	None	None	None	N	0.261	0.099	0.0716867268079	gnomAD-4.0.0	6.8428E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99552E-07	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
N/A	0.1281	likely_benign	0.1401	benign	-1.076	Destabilizing	None	N	0.371	neutral	None	None	None	None	N
N/C	0.1364	likely_benign	0.1559	benign	-0.439	Destabilizing	0.245	N	0.617	neutral	None	None	None	None	N
N/D	0.1202	likely_benign	0.1215	benign	-1.749	Destabilizing	0.007	N	0.399	neutral	N	0.470893578	None	None	N
N/E	0.2672	likely_benign	0.2714	benign	-1.475	Destabilizing	None	N	0.26	neutral	None	None	None	None	N
N/F	0.241	likely_benign	0.2659	benign	-0.438	Destabilizing	0.022	N	0.633	neutral	None	None	None	None	N
N/G	0.1713	likely_benign	0.1858	benign	-1.513	Destabilizing	None	N	0.186	neutral	None	None	None	None	N
N/H	0.0616	likely_benign	0.061	benign	-1.056	Destabilizing	None	N	0.384	neutral	N	0.4654104	None	None	N
N/I	0.1176	likely_benign	0.1196	benign	0.108	Stabilizing	0.033	N	0.627	neutral	N	0.455617481	None	None	N
N/K	0.1561	likely_benign	0.1573	benign	-0.295	Destabilizing	None	N	0.261	neutral	N	0.445168414	None	None	N
N/L	0.1197	likely_benign	0.1266	benign	0.108	Stabilizing	0.009	N	0.547	neutral	None	None	None	None	N
N/M	0.2124	likely_benign	0.2206	benign	0.239	Stabilizing	0.245	N	0.573	neutral	None	None	None	None	N
N/P	0.7192	likely_pathogenic	0.7	pathogenic	-0.259	Destabilizing	0.044	N	0.598	neutral	None	None	None	None	N
N/Q	0.1813	likely_benign	0.1868	benign	-0.795	Destabilizing	0.022	N	0.476	neutral	None	None	None	None	N
N/R	0.1485	likely_benign	0.1438	benign	-0.686	Destabilizing	0.009	N	0.433	neutral	None	None	None	None	N
N/S	0.0622	likely_benign	0.0637	benign	-1.348	Destabilizing	None	N	0.201	neutral	N	0.369169145	None	None	N
N/T	0.0789	likely_benign	0.0843	benign	-0.878	Destabilizing	None	N	0.188	neutral	N	0.388906912	None	None	N
N/V	0.137	likely_benign	0.1407	benign	-0.259	Destabilizing	0.009	N	0.561	neutral	None	None	None	None	N
N/W	0.4613	ambiguous	0.4655	ambiguous	-0.41	Destabilizing	0.55	D	0.617	neutral	None	None	None	None	N
N/Y	0.0828	likely_benign	0.0904	benign	-0.047	Destabilizing	None	N	0.439	neutral	N	0.448614151	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.