TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8529	25810;25811;25812	chr2:178717149;178717148;178717147	chr2:179581876;179581875;179581874
N2AB	8212	24859;24860;24861	chr2:178717149;178717148;178717147	chr2:179581876;179581875;179581874
N2A	7285	22078;22079;22080	chr2:178717149;178717148;178717147	chr2:179581876;179581875;179581874
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: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-70
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.2025
• 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	0.967	N	0.595	0.371	0.595757661845	gnomAD-4.0.0	1.59197E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43316E-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
Y/A	0.2478	likely_benign	0.2218	benign	-2.081	Highly Destabilizing	0.088	N	0.504	neutral	None	None	None	None	I
Y/C	0.124	likely_benign	0.1293	benign	-0.565	Destabilizing	0.967	D	0.595	neutral	N	0.491377549	None	None	I
Y/D	0.2314	likely_benign	0.226	benign	-0.308	Destabilizing	0.15	N	0.532	neutral	N	0.513028202	None	None	I
Y/E	0.4214	ambiguous	0.4081	ambiguous	-0.253	Destabilizing	0.006	N	0.463	neutral	None	None	None	None	I
Y/F	0.0691	likely_benign	0.0669	benign	-0.991	Destabilizing	None	N	0.226	neutral	N	0.482206649	None	None	I
Y/G	0.3382	likely_benign	0.3191	benign	-2.368	Highly Destabilizing	0.162	N	0.519	neutral	None	None	None	None	I
Y/H	0.1025	likely_benign	0.0976	benign	-0.743	Destabilizing	None	N	0.214	neutral	N	0.463178171	None	None	I
Y/I	0.2135	likely_benign	0.2024	benign	-1.237	Destabilizing	0.009	N	0.563	neutral	None	None	None	None	I
Y/K	0.4297	ambiguous	0.4164	ambiguous	-0.672	Destabilizing	0.012	N	0.511	neutral	None	None	None	None	I
Y/L	0.247	likely_benign	0.2303	benign	-1.237	Destabilizing	0.004	N	0.439	neutral	None	None	None	None	I
Y/M	0.3344	likely_benign	0.3121	benign	-0.781	Destabilizing	0.5	D	0.55	neutral	None	None	None	None	I
Y/N	0.1072	likely_benign	0.0983	benign	-0.834	Destabilizing	0.15	N	0.553	neutral	N	0.479184987	None	None	I
Y/P	0.9551	likely_pathogenic	0.9535	pathogenic	-1.51	Destabilizing	0.487	N	0.661	neutral	None	None	None	None	I
Y/Q	0.2553	likely_benign	0.2419	benign	-0.855	Destabilizing	0.005	N	0.339	neutral	None	None	None	None	I
Y/R	0.2789	likely_benign	0.2748	benign	-0.16	Destabilizing	0.163	N	0.58	neutral	None	None	None	None	I
Y/S	0.0898	likely_benign	0.0778	benign	-1.446	Destabilizing	0.014	N	0.465	neutral	N	0.421907552	None	None	I
Y/T	0.1462	likely_benign	0.1278	benign	-1.302	Destabilizing	0.006	N	0.463	neutral	None	None	None	None	I
Y/V	0.1707	likely_benign	0.1596	benign	-1.51	Destabilizing	0.088	N	0.469	neutral	None	None	None	None	I
Y/W	0.3649	ambiguous	0.3749	ambiguous	-0.621	Destabilizing	0.85	D	0.546	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.