TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7203	21832;21833;21834	chr2:178723493;178723492;178723491	chr2:179588220;179588219;179588218
N2AB	6886	20881;20882;20883	chr2:178723493;178723492;178723491	chr2:179588220;179588219;179588218
N2A	5959	18100;18101;18102	chr2:178723493;178723492;178723491	chr2:179588220;179588219;179588218
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-56
• Domain position: 67
• Structural Position: 149
• Q(SASA): 0.1601
• Predicted PPI site: N

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/H	rs1374160884	None	0.002	N	0.371	0.158	0.128392430309	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Q/H	rs1374160884	None	0.002	N	0.371	0.158	0.128392430309	gnomAD-4.0.0	2.47953E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.39098E-06	0	0
Q/P	None	None	0.523	D	0.648	0.38	0.386721274199	gnomAD-4.0.0	2.46701E-05	None	None	None	None	N	None	2.99258E-05	0	None	0	0	None	0	0	3.06336E-05	1.16044E-05	0
Q/R	None	None	0.351	N	0.519	0.298	0.28492961333	gnomAD-4.0.0	6.8526E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00953E-07	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
Q/A	0.2612	likely_benign	0.276	benign	-0.885	Destabilizing	0.061	N	0.557	neutral	None	None	None	None	N
Q/C	0.6439	likely_pathogenic	0.6455	pathogenic	-0.226	Destabilizing	0.983	D	0.76	deleterious	None	None	None	None	N
Q/D	0.2289	likely_benign	0.2076	benign	-0.522	Destabilizing	0.001	N	0.323	neutral	None	None	None	None	N
Q/E	0.0761	likely_benign	0.0768	benign	-0.377	Destabilizing	0.003	N	0.258	neutral	N	0.517703303	None	None	N
Q/F	0.6646	likely_pathogenic	0.655	pathogenic	-0.607	Destabilizing	0.264	N	0.759	deleterious	None	None	None	None	N
Q/G	0.2568	likely_benign	0.2904	benign	-1.266	Destabilizing	0.001	N	0.491	neutral	None	None	None	None	N
Q/H	0.1796	likely_benign	0.1665	benign	-0.951	Destabilizing	0.002	N	0.371	neutral	N	0.475088676	None	None	N
Q/I	0.5027	ambiguous	0.5065	ambiguous	0.105	Stabilizing	0.593	D	0.753	deleterious	None	None	None	None	N
Q/K	0.1435	likely_benign	0.1616	benign	-0.278	Destabilizing	0.183	N	0.457	neutral	N	0.487262946	None	None	N
Q/L	0.1767	likely_benign	0.1731	benign	0.105	Stabilizing	0.183	N	0.664	neutral	N	0.510900609	None	None	N
Q/M	0.4093	ambiguous	0.4038	ambiguous	0.585	Stabilizing	0.94	D	0.602	neutral	None	None	None	None	N
Q/N	0.2313	likely_benign	0.2122	benign	-1.059	Destabilizing	0.001	N	0.336	neutral	None	None	None	None	N
Q/P	0.3114	likely_benign	0.3603	ambiguous	-0.194	Destabilizing	0.523	D	0.648	neutral	D	0.522256915	None	None	N
Q/R	0.1441	likely_benign	0.1599	benign	-0.267	Destabilizing	0.351	N	0.519	neutral	N	0.50389917	None	None	N
Q/S	0.2297	likely_benign	0.2341	benign	-1.214	Destabilizing	0.012	N	0.34	neutral	None	None	None	None	N
Q/T	0.2636	likely_benign	0.284	benign	-0.843	Destabilizing	0.129	N	0.605	neutral	None	None	None	None	N
Q/V	0.3379	likely_benign	0.3413	ambiguous	-0.194	Destabilizing	0.418	N	0.679	prob.neutral	None	None	None	None	N
Q/W	0.489	ambiguous	0.5127	ambiguous	-0.428	Destabilizing	0.983	D	0.745	deleterious	None	None	None	None	N
Q/Y	0.3954	ambiguous	0.3838	ambiguous	-0.202	Destabilizing	0.01	N	0.485	neutral	None	None	None	None	N

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.