TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1343	4252;4253;4254	chr2:178779055;178779054;178779053	chr2:179643782;179643781;179643780
N2AB	1343	4252;4253;4254	chr2:178779055;178779054;178779053	chr2:179643782;179643781;179643780
N2A	1343	4252;4253;4254	chr2:178779055;178779054;178779053	chr2:179643782;179643781;179643780
N2B	1297	4114;4115;4116	chr2:178779055;178779054;178779053	chr2:179643782;179643781;179643780
Novex-1	1297	4114;4115;4116	chr2:178779055;178779054;178779053	chr2:179643782;179643781;179643780
Novex-2	1297	4114;4115;4116	chr2:178779055;178779054;178779053	chr2:179643782;179643781;179643780
Novex-3	1343	4252;4253;4254	chr2:178779055;178779054;178779053	chr2:179643782;179643781;179643780

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Ig-5
• Domain position: 53
• Structural Position: 130
• Q(SASA): 0.8218
• 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/R	None	None	0.004	N	0.206	0.107	0.0762999501168	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	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	0.1818	likely_benign	0.1846	benign	-0.094	Destabilizing	0.25	N	0.279	neutral	None	None	None	None	I
Q/C	0.813	likely_pathogenic	0.814	pathogenic	-0.253	Destabilizing	0.992	D	0.278	neutral	None	None	None	None	I
Q/D	0.3686	ambiguous	0.3795	ambiguous	0.04	Stabilizing	0.447	N	0.199	neutral	None	None	None	None	I
Q/E	0.0979	likely_benign	0.0963	benign	0.014	Stabilizing	0.004	N	0.219	neutral	N	0.360836563	None	None	I
Q/F	0.7884	likely_pathogenic	0.8006	pathogenic	-0.499	Destabilizing	0.972	D	0.254	neutral	None	None	None	None	I
Q/G	0.2849	likely_benign	0.2812	benign	-0.21	Destabilizing	0.617	D	0.309	neutral	None	None	None	None	I
Q/H	0.2296	likely_benign	0.242	benign	0.127	Stabilizing	0.896	D	0.219	neutral	N	0.442386577	None	None	I
Q/I	0.5297	ambiguous	0.5386	ambiguous	0.118	Stabilizing	0.92	D	0.278	neutral	None	None	None	None	I
Q/K	0.1209	likely_benign	0.1199	benign	0.061	Stabilizing	0.201	N	0.249	neutral	N	0.416213694	None	None	I
Q/L	0.1809	likely_benign	0.1896	benign	0.118	Stabilizing	0.549	D	0.315	neutral	N	0.441986755	None	None	I
Q/M	0.4408	ambiguous	0.4468	ambiguous	-0.068	Destabilizing	0.972	D	0.22	neutral	None	None	None	None	I
Q/N	0.2665	likely_benign	0.2766	benign	-0.393	Destabilizing	0.617	D	0.208	neutral	None	None	None	None	I
Q/P	0.0753	likely_benign	0.0768	benign	0.072	Stabilizing	0.002	N	0.158	neutral	N	0.373603382	None	None	I
Q/R	0.1391	likely_benign	0.1394	benign	0.277	Stabilizing	0.004	N	0.206	neutral	N	0.401042052	None	None	I
Q/S	0.1964	likely_benign	0.2022	benign	-0.361	Destabilizing	0.617	D	0.203	neutral	None	None	None	None	I
Q/T	0.2298	likely_benign	0.2313	benign	-0.253	Destabilizing	0.617	D	0.286	neutral	None	None	None	None	I
Q/V	0.3455	ambiguous	0.3479	ambiguous	0.072	Stabilizing	0.617	D	0.297	neutral	None	None	None	None	I
Q/W	0.7309	likely_pathogenic	0.728	pathogenic	-0.587	Destabilizing	0.992	D	0.34	neutral	None	None	None	None	I
Q/Y	0.5839	likely_pathogenic	0.5942	pathogenic	-0.273	Destabilizing	0.972	D	0.245	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.