TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9060	27403;27404;27405	chr2:178712847;178712846;178712845	chr2:179577574;179577573;179577572
N2AB	8743	26452;26453;26454	chr2:178712847;178712846;178712845	chr2:179577574;179577573;179577572
N2A	7816	23671;23672;23673	chr2:178712847;178712846;178712845	chr2:179577574;179577573;179577572
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: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-76
• Domain position: 42
• Structural Position: 59
• Q(SASA): 0.5835
• 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
V/I	None	None	None	D	0.169	0.111	0.391775403332	gnomAD-4.0.0	3.18274E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8583E-06	1.43287E-05	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
V/A	0.1162	likely_benign	0.1243	benign	-0.396	Destabilizing	None	N	0.088	neutral	N	0.480915783	None	None	I
V/C	0.6525	likely_pathogenic	0.6693	pathogenic	-0.73	Destabilizing	0.676	D	0.348	neutral	None	None	None	None	I
V/D	0.1728	likely_benign	0.2012	benign	-0.319	Destabilizing	0.038	N	0.42	neutral	None	None	None	None	I
V/E	0.1335	likely_benign	0.1485	benign	-0.423	Destabilizing	0.001	N	0.237	neutral	N	0.47724076	None	None	I
V/F	0.0928	likely_benign	0.0932	benign	-0.626	Destabilizing	0.038	N	0.391	neutral	None	None	None	None	I
V/G	0.1271	likely_benign	0.1458	benign	-0.507	Destabilizing	0.029	N	0.418	neutral	N	0.501157769	None	None	I
V/H	0.2767	likely_benign	0.2844	benign	-0.051	Destabilizing	0.214	N	0.359	neutral	None	None	None	None	I
V/I	0.0745	likely_benign	0.0716	benign	-0.246	Destabilizing	None	N	0.169	neutral	D	0.525842783	None	None	I
V/K	0.1446	likely_benign	0.1562	benign	-0.455	Destabilizing	0.072	N	0.378	neutral	None	None	None	None	I
V/L	0.0974	likely_benign	0.0993	benign	-0.246	Destabilizing	None	N	0.081	neutral	N	0.462639454	None	None	I
V/M	0.1095	likely_benign	0.111	benign	-0.495	Destabilizing	0.214	N	0.315	neutral	None	None	None	None	I
V/N	0.1557	likely_benign	0.1588	benign	-0.252	Destabilizing	0.214	N	0.416	neutral	None	None	None	None	I
V/P	0.2929	likely_benign	0.3166	benign	-0.264	Destabilizing	0.214	N	0.391	neutral	None	None	None	None	I
V/Q	0.1451	likely_benign	0.1544	benign	-0.456	Destabilizing	0.214	N	0.384	neutral	None	None	None	None	I
V/R	0.1324	likely_benign	0.146	benign	0.021	Stabilizing	0.214	N	0.405	neutral	None	None	None	None	I
V/S	0.1205	likely_benign	0.1252	benign	-0.582	Destabilizing	0.038	N	0.39	neutral	None	None	None	None	I
V/T	0.1278	likely_benign	0.1265	benign	-0.585	Destabilizing	None	N	0.081	neutral	None	None	None	None	I
V/W	0.5323	ambiguous	0.5774	pathogenic	-0.709	Destabilizing	0.676	D	0.363	neutral	None	None	None	None	I
V/Y	0.3172	likely_benign	0.3249	benign	-0.422	Destabilizing	0.002	N	0.203	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.