TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7457	22594;22595;22596	chr2:178722418;178722417;178722416	chr2:179587145;179587144;179587143
N2AB	7140	21643;21644;21645	chr2:178722418;178722417;178722416	chr2:179587145;179587144;179587143
N2A	6213	18862;18863;18864	chr2:178722418;178722417;178722416	chr2:179587145;179587144;179587143
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-59
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.3708
• 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
V/I	rs1365674340	-0.066	0.309	N	0.347	0.139	0.43126412278	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14837E-04	0	None	0	0	None	0	None	0	0	0
V/I	rs1365674340	-0.066	0.309	N	0.347	0.139	0.43126412278	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/I	rs1365674340	-0.066	0.309	N	0.347	0.139	0.43126412278	gnomAD-4.0.0	2.56347E-06	None	None	None	None	N	None	1.69239E-05	0	None	0	0	None	0	0	2.3944E-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
V/A	0.135	likely_benign	0.1348	benign	-0.826	Destabilizing	0.472	N	0.285	neutral	N	0.506851591	None	None	N
V/C	0.6842	likely_pathogenic	0.6399	pathogenic	-0.71	Destabilizing	0.996	D	0.393	neutral	None	None	None	None	N
V/D	0.2075	likely_benign	0.1931	benign	-0.231	Destabilizing	0.59	D	0.366	neutral	None	None	None	None	N
V/E	0.1423	likely_benign	0.1462	benign	-0.254	Destabilizing	0.012	N	0.182	neutral	N	0.443954905	None	None	N
V/F	0.1038	likely_benign	0.0964	benign	-0.62	Destabilizing	0.91	D	0.389	neutral	None	None	None	None	N
V/G	0.1774	likely_benign	0.1736	benign	-1.07	Destabilizing	0.815	D	0.385	neutral	N	0.510123969	None	None	N
V/H	0.3162	likely_benign	0.3024	benign	-0.427	Destabilizing	0.953	D	0.399	neutral	None	None	None	None	N
V/I	0.0686	likely_benign	0.068	benign	-0.291	Destabilizing	0.309	N	0.347	neutral	N	0.506987664	None	None	N
V/K	0.172	likely_benign	0.1661	benign	-0.627	Destabilizing	0.59	D	0.343	neutral	None	None	None	None	N
V/L	0.131	likely_benign	0.1272	benign	-0.291	Destabilizing	0.007	N	0.136	neutral	D	0.525034707	None	None	N
V/M	0.0976	likely_benign	0.0984	benign	-0.417	Destabilizing	0.91	D	0.401	neutral	None	None	None	None	N
V/N	0.1355	likely_benign	0.1336	benign	-0.535	Destabilizing	0.953	D	0.395	neutral	None	None	None	None	N
V/P	0.797	likely_pathogenic	0.7693	pathogenic	-0.433	Destabilizing	0.984	D	0.391	neutral	None	None	None	None	N
V/Q	0.1514	likely_benign	0.1516	benign	-0.651	Destabilizing	0.101	N	0.234	neutral	None	None	None	None	N
V/R	0.1601	likely_benign	0.152	benign	-0.171	Destabilizing	0.91	D	0.399	neutral	None	None	None	None	N
V/S	0.1357	likely_benign	0.1361	benign	-1.032	Destabilizing	0.742	D	0.347	neutral	None	None	None	None	N
V/T	0.1434	likely_benign	0.1422	benign	-0.938	Destabilizing	0.742	D	0.262	neutral	None	None	None	None	N
V/W	0.6851	likely_pathogenic	0.6543	pathogenic	-0.761	Destabilizing	0.996	D	0.437	neutral	None	None	None	None	N
V/Y	0.3588	ambiguous	0.3327	benign	-0.454	Destabilizing	0.953	D	0.393	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.