TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31891	95896;95897;95898	chr2:178545439;178545438;178545437	chr2:179410166;179410165;179410164
N2AB	30250	90973;90974;90975	chr2:178545439;178545438;178545437	chr2:179410166;179410165;179410164
N2A	29323	88192;88193;88194	chr2:178545439;178545438;178545437	chr2:179410166;179410165;179410164
N2B	22826	68701;68702;68703	chr2:178545439;178545438;178545437	chr2:179410166;179410165;179410164
Novex-1	22951	69076;69077;69078	chr2:178545439;178545438;178545437	chr2:179410166;179410165;179410164
Novex-2	23018	69277;69278;69279	chr2:178545439;178545438;178545437	chr2:179410166;179410165;179410164
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-120
• Domain position: 85
• Structural Position: 117
• Q(SASA): 0.6892
• 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
N/D	rs1351753792	0.19	0.035	N	0.184	0.138	0.128392430309	gnomAD-2.1.1	8.1E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
N/D	rs1351753792	0.19	0.035	N	0.184	0.138	0.128392430309	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
N/D	rs1351753792	0.19	0.035	N	0.184	0.138	0.128392430309	gnomAD-4.0.0	6.57039E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.4699E-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
N/A	0.1727	likely_benign	0.1774	benign	-0.851	Destabilizing	0.863	D	0.512	neutral	None	None	None	None	I
N/C	0.172	likely_benign	0.1717	benign	0.061	Stabilizing	0.999	D	0.523	neutral	None	None	None	None	I
N/D	0.1517	likely_benign	0.1421	benign	-0.235	Destabilizing	0.035	N	0.184	neutral	N	0.434652271	None	None	I
N/E	0.304	likely_benign	0.2916	benign	-0.217	Destabilizing	0.759	D	0.433	neutral	None	None	None	None	I
N/F	0.359	ambiguous	0.3332	benign	-0.923	Destabilizing	0.991	D	0.532	neutral	None	None	None	None	I
N/G	0.2996	likely_benign	0.305	benign	-1.101	Destabilizing	0.927	D	0.435	neutral	None	None	None	None	I
N/H	0.1064	likely_benign	0.1053	benign	-0.941	Destabilizing	0.988	D	0.538	neutral	N	0.46191623	None	None	I
N/I	0.1262	likely_benign	0.1248	benign	-0.249	Destabilizing	0.852	D	0.543	neutral	N	0.329159602	None	None	I
N/K	0.2884	likely_benign	0.2693	benign	-0.127	Destabilizing	0.852	D	0.397	neutral	N	0.383415374	None	None	I
N/L	0.1701	likely_benign	0.1681	benign	-0.249	Destabilizing	0.884	D	0.503	neutral	None	None	None	None	I
N/M	0.2492	likely_benign	0.2437	benign	0.319	Stabilizing	0.991	D	0.532	neutral	None	None	None	None	I
N/P	0.3282	likely_benign	0.3265	benign	-0.422	Destabilizing	0.997	D	0.524	neutral	None	None	None	None	I
N/Q	0.2735	likely_benign	0.2721	benign	-0.778	Destabilizing	0.373	N	0.245	neutral	None	None	None	None	I
N/R	0.3271	likely_benign	0.3131	benign	-0.014	Destabilizing	0.939	D	0.505	neutral	None	None	None	None	I
N/S	0.0872	likely_benign	0.0899	benign	-0.622	Destabilizing	0.704	D	0.453	neutral	N	0.402694568	None	None	I
N/T	0.1101	likely_benign	0.1153	benign	-0.429	Destabilizing	0.134	N	0.191	neutral	N	0.382858013	None	None	I
N/V	0.1377	likely_benign	0.1389	benign	-0.422	Destabilizing	0.17	N	0.44	neutral	None	None	None	None	I
N/W	0.6733	likely_pathogenic	0.6459	pathogenic	-0.693	Destabilizing	0.999	D	0.574	neutral	None	None	None	None	I
N/Y	0.1263	likely_benign	0.1161	benign	-0.503	Destabilizing	0.996	D	0.536	neutral	N	0.419914892	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.