TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7392	22399;22400;22401	chr2:178722725;178722724;178722723	chr2:179587452;179587451;179587450
N2AB	7075	21448;21449;21450	chr2:178722725;178722724;178722723	chr2:179587452;179587451;179587450
N2A	6148	18667;18668;18669	chr2:178722725;178722724;178722723	chr2:179587452;179587451;179587450
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-58
• Domain position: 70
• Structural Position: 153
• Q(SASA): 0.4529
• 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
E/D	rs2078620935	None	0.988	N	0.488	0.265	0.231873229951	gnomAD-4.0.0	2.05348E-06	None	None	None	None	N	None	8.97076E-05	0	None	0	0	None	0	0	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
E/A	0.1194	likely_benign	0.1466	benign	-1.081	Destabilizing	0.811	D	0.387	neutral	D	0.523746628	None	None	N
E/C	0.7653	likely_pathogenic	0.8372	pathogenic	-0.469	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
E/D	0.1192	likely_benign	0.1331	benign	-1.011	Destabilizing	0.988	D	0.488	neutral	N	0.482073363	None	None	N
E/F	0.522	ambiguous	0.6159	pathogenic	-0.538	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
E/G	0.1747	likely_benign	0.2304	benign	-1.43	Destabilizing	0.999	D	0.651	neutral	N	0.503787493	None	None	N
E/H	0.344	ambiguous	0.4285	ambiguous	-0.725	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
E/I	0.174	likely_benign	0.2072	benign	-0.13	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
E/K	0.1239	likely_benign	0.1578	benign	-0.473	Destabilizing	0.999	D	0.523	neutral	N	0.482686652	None	None	N
E/L	0.2307	likely_benign	0.2933	benign	-0.13	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
E/M	0.2792	likely_benign	0.3453	ambiguous	0.381	Stabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
E/N	0.1854	likely_benign	0.2259	benign	-1.002	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
E/P	0.4656	ambiguous	0.5689	pathogenic	-0.427	Destabilizing	0.997	D	0.769	deleterious	None	None	None	None	N
E/Q	0.1164	likely_benign	0.1376	benign	-0.893	Destabilizing	1.0	D	0.625	neutral	N	0.50687302	None	None	N
E/R	0.2104	likely_benign	0.2729	benign	-0.208	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	N
E/S	0.1551	likely_benign	0.1903	benign	-1.308	Destabilizing	0.995	D	0.522	neutral	None	None	None	None	N
E/T	0.1447	likely_benign	0.174	benign	-1.008	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
E/V	0.1189	likely_benign	0.1386	benign	-0.427	Destabilizing	0.999	D	0.707	prob.neutral	N	0.45944722	None	None	N
E/W	0.7646	likely_pathogenic	0.8402	pathogenic	-0.209	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/Y	0.4259	ambiguous	0.5244	ambiguous	-0.253	Destabilizing	1.0	D	0.778	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.