TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4898	14917;14918;14919	chr2:178735754;178735753;178735752	chr2:179600481;179600480;179600479
N2AB	4581	13966;13967;13968	chr2:178735754;178735753;178735752	chr2:179600481;179600480;179600479
N2A	3654	11185;11186;11187	chr2:178735754;178735753;178735752	chr2:179600481;179600480;179600479
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: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-32
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.5392
• 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
Q/L	None	None	0.425	N	0.29	0.255	0.505028829284	gnomAD-4.0.0	1.59143E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85814E-06	0	0
Q/R	rs763540495	0.602	0.006	N	0.169	0.162	0.18274738541	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
Q/R	rs763540495	0.602	0.006	N	0.169	0.162	0.18274738541	gnomAD-4.0.0	1.59143E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43279E-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
Q/A	0.2498	likely_benign	0.2179	benign	-0.151	Destabilizing	0.013	N	0.147	neutral	None	None	None	None	I
Q/C	0.6534	likely_pathogenic	0.5497	ambiguous	0.181	Stabilizing	0.981	D	0.263	neutral	None	None	None	None	I
Q/D	0.4081	ambiguous	0.3535	ambiguous	0.138	Stabilizing	0.495	N	0.193	neutral	None	None	None	None	I
Q/E	0.0852	likely_benign	0.0815	benign	0.098	Stabilizing	0.425	N	0.199	neutral	N	0.48068689	None	None	I
Q/F	0.6292	likely_pathogenic	0.5465	ambiguous	-0.423	Destabilizing	0.981	D	0.3	neutral	None	None	None	None	I
Q/G	0.3509	ambiguous	0.2982	benign	-0.312	Destabilizing	0.495	N	0.256	neutral	None	None	None	None	I
Q/H	0.2229	likely_benign	0.1729	benign	-0.254	Destabilizing	0.927	D	0.288	neutral	N	0.477782561	None	None	I
Q/I	0.3292	likely_benign	0.2858	benign	0.177	Stabilizing	0.704	D	0.382	neutral	None	None	None	None	I
Q/K	0.1187	likely_benign	0.1044	benign	0.182	Stabilizing	0.01	N	0.175	neutral	N	0.492110608	None	None	I
Q/L	0.1421	likely_benign	0.126	benign	0.177	Stabilizing	0.425	N	0.29	neutral	N	0.503085515	None	None	I
Q/M	0.399	ambiguous	0.3527	ambiguous	0.402	Stabilizing	0.981	D	0.289	neutral	None	None	None	None	I
Q/N	0.3125	likely_benign	0.2742	benign	-0.127	Destabilizing	0.495	N	0.195	neutral	None	None	None	None	I
Q/P	0.174	likely_benign	0.1587	benign	0.095	Stabilizing	0.784	D	0.322	neutral	N	0.512318323	None	None	I
Q/R	0.1232	likely_benign	0.1052	benign	0.291	Stabilizing	0.006	N	0.169	neutral	N	0.397192716	None	None	I
Q/S	0.2623	likely_benign	0.2254	benign	-0.13	Destabilizing	0.037	N	0.146	neutral	None	None	None	None	I
Q/T	0.1987	likely_benign	0.1694	benign	-0.018	Destabilizing	0.013	N	0.161	neutral	None	None	None	None	I
Q/V	0.239	likely_benign	0.208	benign	0.095	Stabilizing	0.495	N	0.295	neutral	None	None	None	None	I
Q/W	0.5162	ambiguous	0.4052	ambiguous	-0.415	Destabilizing	0.995	D	0.264	neutral	None	None	None	None	I
Q/Y	0.4089	ambiguous	0.3275	benign	-0.142	Destabilizing	0.981	D	0.338	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.