TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18633	56122;56123;56124	chr2:178601007;178601006;178601005	chr2:179465734;179465733;179465732
N2AB	16992	51199;51200;51201	chr2:178601007;178601006;178601005	chr2:179465734;179465733;179465732
N2A	16065	48418;48419;48420	chr2:178601007;178601006;178601005	chr2:179465734;179465733;179465732
N2B	9568	28927;28928;28929	chr2:178601007;178601006;178601005	chr2:179465734;179465733;179465732
Novex-1	9693	29302;29303;29304	chr2:178601007;178601006;178601005	chr2:179465734;179465733;179465732
Novex-2	9760	29503;29504;29505	chr2:178601007;178601006;178601005	chr2:179465734;179465733;179465732
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: Fn3-23
• Domain position: 55
• Structural Position: 67
• Q(SASA): 0.3564
• 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/H	None	None	0.999	N	0.691	0.226	0.250039746154	gnomAD-4.0.0	6.84467E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99753E-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	0.2646	likely_benign	0.2682	benign	-0.471	Destabilizing	0.997	D	0.548	neutral	None	None	None	None	I
Q/C	0.7755	likely_pathogenic	0.8226	pathogenic	0.148	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
Q/D	0.7053	likely_pathogenic	0.7792	pathogenic	-0.4	Destabilizing	0.997	D	0.537	neutral	None	None	None	None	I
Q/E	0.1429	likely_benign	0.1619	benign	-0.371	Destabilizing	0.992	D	0.379	neutral	N	0.453387173	None	None	I
Q/F	0.7952	likely_pathogenic	0.8443	pathogenic	-0.394	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	I
Q/G	0.4943	ambiguous	0.5394	ambiguous	-0.76	Destabilizing	0.997	D	0.647	neutral	None	None	None	None	I
Q/H	0.4517	ambiguous	0.5244	ambiguous	-0.742	Destabilizing	0.999	D	0.691	prob.neutral	N	0.502490629	None	None	I
Q/I	0.3497	ambiguous	0.4072	ambiguous	0.229	Stabilizing	0.999	D	0.795	deleterious	None	None	None	None	I
Q/K	0.1616	likely_benign	0.2015	benign	-0.255	Destabilizing	0.997	D	0.468	neutral	N	0.44733078	None	None	I
Q/L	0.174	likely_benign	0.2098	benign	0.229	Stabilizing	0.997	D	0.647	neutral	N	0.466148614	None	None	I
Q/M	0.4071	ambiguous	0.4312	ambiguous	0.727	Stabilizing	0.999	D	0.692	prob.neutral	None	None	None	None	I
Q/N	0.4627	ambiguous	0.5328	ambiguous	-0.668	Destabilizing	0.999	D	0.643	neutral	None	None	None	None	I
Q/P	0.1217	likely_benign	0.1325	benign	0.027	Stabilizing	0.999	D	0.78	deleterious	N	0.444349189	None	None	I
Q/R	0.1708	likely_benign	0.2095	benign	-0.128	Destabilizing	0.997	D	0.509	neutral	N	0.438807297	None	None	I
Q/S	0.3981	ambiguous	0.429	ambiguous	-0.7	Destabilizing	0.997	D	0.487	neutral	None	None	None	None	I
Q/T	0.2727	likely_benign	0.3193	benign	-0.496	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	I
Q/V	0.2425	likely_benign	0.2853	benign	0.027	Stabilizing	0.999	D	0.714	prob.delet.	None	None	None	None	I
Q/W	0.7721	likely_pathogenic	0.8462	pathogenic	-0.304	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
Q/Y	0.6816	likely_pathogenic	0.7641	pathogenic	-0.086	Destabilizing	0.999	D	0.793	deleterious	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.