TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23408	70447;70448;70449	chr2:178575910;178575909;178575908	chr2:179440637;179440636;179440635
N2AB	21767	65524;65525;65526	chr2:178575910;178575909;178575908	chr2:179440637;179440636;179440635
N2A	20840	62743;62744;62745	chr2:178575910;178575909;178575908	chr2:179440637;179440636;179440635
N2B	14343	43252;43253;43254	chr2:178575910;178575909;178575908	chr2:179440637;179440636;179440635
Novex-1	14468	43627;43628;43629	chr2:178575910;178575909;178575908	chr2:179440637;179440636;179440635
Novex-2	14535	43828;43829;43830	chr2:178575910;178575909;178575908	chr2:179440637;179440636;179440635
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-129
• Domain position: 64
• Structural Position: 148
• Q(SASA): 0.9553
• 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
Y/C	None	None	0.99	N	0.445	0.337	0.414021929199	gnomAD-4.0.0	1.59164E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8593E-06	0	0
Y/H	rs754261585	0.796	0.81	N	0.465	0.227	0.204665344411	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
Y/H	rs754261585	0.796	0.81	N	0.465	0.227	0.204665344411	gnomAD-4.0.0	2.05284E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79916E-06	0	1.65678E-05

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
Y/A	0.4565	ambiguous	0.4672	ambiguous	-0.405	Destabilizing	0.617	D	0.489	neutral	None	None	None	None	I
Y/C	0.226	likely_benign	0.2444	benign	0.19	Stabilizing	0.99	D	0.445	neutral	N	0.489800973	None	None	I
Y/D	0.2164	likely_benign	0.2326	benign	1.022	Stabilizing	0.004	N	0.379	neutral	N	0.416089861	None	None	I
Y/E	0.506	ambiguous	0.5501	ambiguous	0.995	Stabilizing	0.447	N	0.496	neutral	None	None	None	None	I
Y/F	0.1085	likely_benign	0.1129	benign	-0.243	Destabilizing	0.549	D	0.489	neutral	N	0.452186734	None	None	I
Y/G	0.3897	ambiguous	0.4217	ambiguous	-0.567	Destabilizing	0.447	N	0.481	neutral	None	None	None	None	I
Y/H	0.1504	likely_benign	0.1835	benign	0.293	Stabilizing	0.81	D	0.465	neutral	N	0.455611041	None	None	I
Y/I	0.5793	likely_pathogenic	0.61	pathogenic	-0.016	Destabilizing	0.447	N	0.462	neutral	None	None	None	None	I
Y/K	0.5027	ambiguous	0.5912	pathogenic	0.362	Stabilizing	0.447	N	0.451	neutral	None	None	None	None	I
Y/L	0.4417	ambiguous	0.4756	ambiguous	-0.016	Destabilizing	0.005	N	0.323	neutral	None	None	None	None	I
Y/M	0.5449	ambiguous	0.557	ambiguous	0.048	Stabilizing	0.85	D	0.441	neutral	None	None	None	None	I
Y/N	0.0985	likely_benign	0.1004	benign	0.189	Stabilizing	0.004	N	0.343	neutral	N	0.439678796	None	None	I
Y/P	0.9397	likely_pathogenic	0.9389	pathogenic	-0.125	Destabilizing	0.92	D	0.444	neutral	None	None	None	None	I
Y/Q	0.3832	ambiguous	0.4532	ambiguous	0.253	Stabilizing	0.85	D	0.447	neutral	None	None	None	None	I
Y/R	0.3169	likely_benign	0.4332	ambiguous	0.525	Stabilizing	0.85	D	0.46	neutral	None	None	None	None	I
Y/S	0.1956	likely_benign	0.1983	benign	-0.217	Destabilizing	0.379	N	0.488	neutral	N	0.392711569	None	None	I
Y/T	0.382	ambiguous	0.3972	ambiguous	-0.151	Destabilizing	0.617	D	0.464	neutral	None	None	None	None	I
Y/V	0.4724	ambiguous	0.4976	ambiguous	-0.125	Destabilizing	0.447	N	0.479	neutral	None	None	None	None	I
Y/W	0.4331	ambiguous	0.4916	ambiguous	-0.46	Destabilizing	0.992	D	0.471	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.