TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2959	9100;9101;9102	chr2:178769706;178769705;178769704	chr2:179634433;179634432;179634431
N2AB	2959	9100;9101;9102	chr2:178769706;178769705;178769704	chr2:179634433;179634432;179634431
N2A	2959	9100;9101;9102	chr2:178769706;178769705;178769704	chr2:179634433;179634432;179634431
N2B	2913	8962;8963;8964	chr2:178769706;178769705;178769704	chr2:179634433;179634432;179634431
Novex-1	2913	8962;8963;8964	chr2:178769706;178769705;178769704	chr2:179634433;179634432;179634431
Novex-2	2913	8962;8963;8964	chr2:178769706;178769705;178769704	chr2:179634433;179634432;179634431
Novex-3	2959	9100;9101;9102	chr2:178769706;178769705;178769704	chr2:179634433;179634432;179634431

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Ig-19
• Domain position: 78
• Structural Position: 163
• Q(SASA): 0.3133
• 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/L	rs2091182281	None	0.425	N	0.539	0.279	0.432716982437	gnomAD-4.0.0	3.18334E-06	None	None	None	None	N	None	0	0	None	0	5.55093E-05	None	0	0	0	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	0.2746	likely_benign	0.3366	benign	-0.269	Destabilizing	0.3	N	0.449	neutral	None	None	None	None	N
Q/C	0.6249	likely_pathogenic	0.6928	pathogenic	0.126	Stabilizing	0.995	D	0.474	neutral	None	None	None	None	N
Q/D	0.6305	likely_pathogenic	0.7292	pathogenic	0.01	Stabilizing	0.495	N	0.403	neutral	None	None	None	None	N
Q/E	0.1096	likely_benign	0.1187	benign	0.016	Stabilizing	0.139	N	0.314	neutral	N	0.449501153	None	None	N
Q/F	0.7733	likely_pathogenic	0.8408	pathogenic	-0.304	Destabilizing	0.981	D	0.484	neutral	None	None	None	None	N
Q/G	0.4591	ambiguous	0.5252	ambiguous	-0.511	Destabilizing	0.495	N	0.539	neutral	None	None	None	None	N
Q/H	0.1898	likely_benign	0.2746	benign	-0.396	Destabilizing	0.927	D	0.419	neutral	N	0.502403187	None	None	N
Q/I	0.4595	ambiguous	0.528	ambiguous	0.293	Stabilizing	0.944	D	0.504	neutral	None	None	None	None	N
Q/K	0.0676	likely_benign	0.0876	benign	0.023	Stabilizing	0.001	N	0.285	neutral	N	0.400513643	None	None	N
Q/L	0.2273	likely_benign	0.2807	benign	0.293	Stabilizing	0.425	N	0.539	neutral	N	0.502535969	None	None	N
Q/M	0.3936	ambiguous	0.4539	ambiguous	0.525	Stabilizing	0.981	D	0.419	neutral	None	None	None	None	N
Q/N	0.4027	ambiguous	0.5068	ambiguous	-0.403	Destabilizing	0.495	N	0.401	neutral	None	None	None	None	N
Q/P	0.6961	likely_pathogenic	0.8084	pathogenic	0.136	Stabilizing	0.784	D	0.509	neutral	N	0.503150077	None	None	N
Q/R	0.0798	likely_benign	0.0988	benign	0.135	Stabilizing	0.001	N	0.278	neutral	N	0.40864693	None	None	N
Q/S	0.3186	likely_benign	0.3889	ambiguous	-0.412	Destabilizing	0.495	N	0.389	neutral	None	None	None	None	N
Q/T	0.1881	likely_benign	0.2345	benign	-0.233	Destabilizing	0.495	N	0.476	neutral	None	None	None	None	N
Q/V	0.3041	likely_benign	0.3629	ambiguous	0.136	Stabilizing	0.828	D	0.521	neutral	None	None	None	None	N
Q/W	0.6504	likely_pathogenic	0.7488	pathogenic	-0.237	Destabilizing	0.995	D	0.493	neutral	None	None	None	None	N
Q/Y	0.5468	ambiguous	0.6594	pathogenic	0.007	Stabilizing	0.981	D	0.491	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.