TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25763	77512;77513;77514	chr2:178568845;178568844;178568843	chr2:179433572;179433571;179433570
N2AB	24122	72589;72590;72591	chr2:178568845;178568844;178568843	chr2:179433572;179433571;179433570
N2A	23195	69808;69809;69810	chr2:178568845;178568844;178568843	chr2:179433572;179433571;179433570
N2B	16698	50317;50318;50319	chr2:178568845;178568844;178568843	chr2:179433572;179433571;179433570
Novex-1	16823	50692;50693;50694	chr2:178568845;178568844;178568843	chr2:179433572;179433571;179433570
Novex-2	16890	50893;50894;50895	chr2:178568845;178568844;178568843	chr2:179433572;179433571;179433570
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Fn3-75
• Domain position: 66
• Structural Position: 99
• Q(SASA): 0.3894
• 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/K	None	None	0.09	N	0.112	0.132	0.158396225186	gnomAD-4.0.0	1.5929E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.89415E-05	0	0	0	0
Q/P	None	None	0.997	N	0.418	0.424	0.230578612272	gnomAD-4.0.0	2.73845E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69941E-06	0	1.65733E-05
Q/R	None	None	0.852	N	0.463	0.239	0.193865811164	gnomAD-4.0.0	6.84584E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99756E-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	0.1222	likely_benign	0.1095	benign	-0.312	Destabilizing	0.983	D	0.411	neutral	None	None	None	None	N
Q/C	0.7158	likely_pathogenic	0.6753	pathogenic	0.266	Stabilizing	0.999	D	0.624	neutral	None	None	None	None	N
Q/D	0.4886	ambiguous	0.4301	ambiguous	-0.196	Destabilizing	0.973	D	0.433	neutral	None	None	None	None	N
Q/E	0.0745	likely_benign	0.0706	benign	-0.218	Destabilizing	0.883	D	0.505	neutral	N	0.383375302	None	None	N
Q/F	0.7614	likely_pathogenic	0.7169	pathogenic	-0.435	Destabilizing	0.999	D	0.59	neutral	None	None	None	None	N
Q/G	0.2954	likely_benign	0.2602	benign	-0.53	Destabilizing	0.992	D	0.479	neutral	None	None	None	None	N
Q/H	0.2869	likely_benign	0.2569	benign	-0.508	Destabilizing	0.997	D	0.407	neutral	N	0.48636917	None	None	N
Q/I	0.3854	ambiguous	0.353	ambiguous	0.183	Stabilizing	0.998	D	0.579	neutral	None	None	None	None	N
Q/K	0.114	likely_benign	0.1096	benign	-0.028	Destabilizing	0.09	N	0.112	neutral	N	0.44546391	None	None	N
Q/L	0.1749	likely_benign	0.1601	benign	0.183	Stabilizing	0.973	D	0.479	neutral	N	0.492391066	None	None	N
Q/M	0.356	ambiguous	0.3286	benign	0.596	Stabilizing	0.998	D	0.405	neutral	None	None	None	None	N
Q/N	0.3583	ambiguous	0.326	benign	-0.299	Destabilizing	0.973	D	0.441	neutral	None	None	None	None	N
Q/P	0.0928	likely_benign	0.083	benign	0.047	Stabilizing	0.997	D	0.418	neutral	N	0.350942304	None	None	N
Q/R	0.1341	likely_benign	0.129	benign	0.141	Stabilizing	0.852	D	0.463	neutral	N	0.467436693	None	None	N
Q/S	0.2105	likely_benign	0.1897	benign	-0.312	Destabilizing	0.983	D	0.419	neutral	None	None	None	None	N
Q/T	0.188	likely_benign	0.1653	benign	-0.177	Destabilizing	0.821	D	0.445	neutral	None	None	None	None	N
Q/V	0.2109	likely_benign	0.1918	benign	0.047	Stabilizing	0.98	D	0.455	neutral	None	None	None	None	N
Q/W	0.7034	likely_pathogenic	0.6604	pathogenic	-0.377	Destabilizing	1.0	D	0.605	neutral	None	None	None	None	N
Q/Y	0.5809	likely_pathogenic	0.534	ambiguous	-0.142	Destabilizing	0.999	D	0.426	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.