TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15560	46903;46904;46905	chr2:178619639;178619638;178619637	chr2:179484366;179484365;179484364
N2AB	13919	41980;41981;41982	chr2:178619639;178619638;178619637	chr2:179484366;179484365;179484364
N2A	12992	39199;39200;39201	chr2:178619639;178619638;178619637	chr2:179484366;179484365;179484364
N2B	6495	19708;19709;19710	chr2:178619639;178619638;178619637	chr2:179484366;179484365;179484364
Novex-1	6620	20083;20084;20085	chr2:178619639;178619638;178619637	chr2:179484366;179484365;179484364
Novex-2	6687	20284;20285;20286	chr2:178619639;178619638;178619637	chr2:179484366;179484365;179484364
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-107
• Domain position: 81
• Structural Position: 172
• Q(SASA): 0.1841
• 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
A/G	rs2057972776	None	1.0	D	0.559	0.45	0.483741690565	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	9.43E-05	0	0	0	0
A/G	rs2057972776	None	1.0	D	0.559	0.45	0.483741690565	gnomAD-4.0.0	6.58467E-06	None	None	None	None	N	None	0	0	None	0	0	None	9.42863E-05	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
A/C	0.7124	likely_pathogenic	0.6474	pathogenic	-1.019	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
A/D	0.9927	likely_pathogenic	0.9923	pathogenic	-2.222	Highly Destabilizing	1.0	D	0.822	deleterious	D	0.642317686	None	None	N
A/E	0.9899	likely_pathogenic	0.9889	pathogenic	-2.047	Highly Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
A/F	0.9761	likely_pathogenic	0.9668	pathogenic	-0.757	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
A/G	0.249	likely_benign	0.2337	benign	-1.587	Destabilizing	1.0	D	0.559	neutral	D	0.602366369	None	None	N
A/H	0.9929	likely_pathogenic	0.9903	pathogenic	-2.016	Highly Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
A/I	0.953	likely_pathogenic	0.9408	pathogenic	0.119	Stabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
A/K	0.9959	likely_pathogenic	0.9948	pathogenic	-1.31	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
A/L	0.908	likely_pathogenic	0.883	pathogenic	0.119	Stabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
A/M	0.9374	likely_pathogenic	0.92	pathogenic	0.01	Stabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
A/N	0.9832	likely_pathogenic	0.9785	pathogenic	-1.499	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
A/P	0.9941	likely_pathogenic	0.9951	pathogenic	-0.25	Destabilizing	1.0	D	0.811	deleterious	D	0.642317686	None	None	N
A/Q	0.9785	likely_pathogenic	0.9731	pathogenic	-1.347	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
A/R	0.9859	likely_pathogenic	0.9821	pathogenic	-1.323	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
A/S	0.3284	likely_benign	0.307	benign	-1.919	Destabilizing	1.0	D	0.565	neutral	D	0.59848087	None	None	N
A/T	0.6558	likely_pathogenic	0.6142	pathogenic	-1.622	Destabilizing	1.0	D	0.663	neutral	D	0.594898944	None	None	N
A/V	0.7584	likely_pathogenic	0.7242	pathogenic	-0.25	Destabilizing	1.0	D	0.572	neutral	D	0.640735517	None	None	N
A/W	0.9977	likely_pathogenic	0.9969	pathogenic	-1.529	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
A/Y	0.9912	likely_pathogenic	0.9881	pathogenic	-0.963	Destabilizing	1.0	D	0.851	deleterious	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.