TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7339	22240;22241;22242	chr2:178722884;178722883;178722882	chr2:179587611;179587610;179587609
N2AB	7022	21289;21290;21291	chr2:178722884;178722883;178722882	chr2:179587611;179587610;179587609
N2A	6095	18508;18509;18510	chr2:178722884;178722883;178722882	chr2:179587611;179587610;179587609
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: S
• RefSeq wild type transcript codon: TCG
• RefSeq wild type template codon: AGC
• Domain: Ig-58
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.5193
• 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
S/L	rs72648966	-0.284	0.064	N	0.382	0.146	None	gnomAD-2.1.1	2.02E-05	None	None	None	None	I	None	0	0	None	0	5.63E-05	None	0	None	0	2.68E-05	1.67448E-04
S/L	rs72648966	-0.284	0.064	N	0.382	0.146	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
S/L	rs72648966	-0.284	0.064	N	0.382	0.146	None	gnomAD-4.0.0	9.92094E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	1.64636E-04	1.27187E-05	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
S/A	0.0684	likely_benign	0.0817	benign	-0.295	Destabilizing	None	N	0.158	neutral	N	0.458115415	None	None	I
S/C	0.1532	likely_benign	0.2239	benign	-0.276	Destabilizing	0.676	D	0.391	neutral	None	None	None	None	I
S/D	0.3948	ambiguous	0.557	ambiguous	0.214	Stabilizing	0.038	N	0.22	neutral	None	None	None	None	I
S/E	0.5263	ambiguous	0.6735	pathogenic	0.131	Stabilizing	0.072	N	0.22	neutral	None	None	None	None	I
S/F	0.1555	likely_benign	0.241	benign	-0.829	Destabilizing	0.12	N	0.468	neutral	None	None	None	None	I
S/G	0.1214	likely_benign	0.1636	benign	-0.426	Destabilizing	0.016	N	0.3	neutral	None	None	None	None	I
S/H	0.3373	likely_benign	0.4643	ambiguous	-0.894	Destabilizing	0.214	N	0.402	neutral	None	None	None	None	I
S/I	0.1572	likely_benign	0.2328	benign	-0.082	Destabilizing	0.038	N	0.415	neutral	None	None	None	None	I
S/K	0.6187	likely_pathogenic	0.7881	pathogenic	-0.436	Destabilizing	0.072	N	0.225	neutral	None	None	None	None	I
S/L	0.0916	likely_benign	0.1233	benign	-0.082	Destabilizing	0.064	N	0.382	neutral	N	0.495094936	None	None	I
S/M	0.2013	likely_benign	0.2551	benign	0.083	Stabilizing	0.356	N	0.403	neutral	None	None	None	None	I
S/N	0.1573	likely_benign	0.2088	benign	-0.189	Destabilizing	0.001	N	0.199	neutral	None	None	None	None	I
S/P	0.1074	likely_benign	0.1481	benign	-0.123	Destabilizing	0.295	N	0.445	neutral	N	0.441721811	None	None	I
S/Q	0.4845	ambiguous	0.6171	pathogenic	-0.418	Destabilizing	0.356	N	0.349	neutral	None	None	None	None	I
S/R	0.5208	ambiguous	0.7031	pathogenic	-0.232	Destabilizing	0.214	N	0.444	neutral	None	None	None	None	I
S/T	0.0826	likely_benign	0.0976	benign	-0.29	Destabilizing	None	N	0.175	neutral	N	0.449493145	None	None	I
S/V	0.1496	likely_benign	0.2117	benign	-0.123	Destabilizing	0.001	N	0.271	neutral	None	None	None	None	I
S/W	0.3302	likely_benign	0.4842	ambiguous	-0.845	Destabilizing	0.8	D	0.441	neutral	N	0.495614062	None	None	I
S/Y	0.1431	likely_benign	0.2199	benign	-0.554	Destabilizing	None	N	0.29	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.