TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9292	28099;28100;28101	chr2:178711956;178711955;178711954	chr2:179576683;179576682;179576681
N2AB	8975	27148;27149;27150	chr2:178711956;178711955;178711954	chr2:179576683;179576682;179576681
N2A	8048	24367;24368;24369	chr2:178711956;178711955;178711954	chr2:179576683;179576682;179576681
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-78
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.1564
• 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
L/F	None	None	0.999	N	0.809	0.498	0.583773441324	gnomAD-4.0.0	1.62989E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.92677E-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
L/A	0.9159	likely_pathogenic	0.9499	pathogenic	-2.692	Highly Destabilizing	0.997	D	0.698	prob.neutral	None	None	None	None	N
L/C	0.8266	likely_pathogenic	0.8979	pathogenic	-2.076	Highly Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
L/D	0.9981	likely_pathogenic	0.9991	pathogenic	-3.024	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
L/E	0.9902	likely_pathogenic	0.9944	pathogenic	-2.717	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
L/F	0.155	likely_benign	0.2357	benign	-1.607	Destabilizing	0.999	D	0.809	deleterious	N	0.504500919	None	None	N
L/G	0.9835	likely_pathogenic	0.9912	pathogenic	-3.321	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
L/H	0.9365	likely_pathogenic	0.9699	pathogenic	-2.9	Highly Destabilizing	1.0	D	0.888	deleterious	D	0.557941538	None	None	N
L/I	0.1211	likely_benign	0.146	benign	-0.828	Destabilizing	0.992	D	0.666	neutral	N	0.49742012	None	None	N
L/K	0.9836	likely_pathogenic	0.9891	pathogenic	-2.023	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
L/M	0.2491	likely_benign	0.3122	benign	-0.964	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
L/N	0.9902	likely_pathogenic	0.994	pathogenic	-2.6	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
L/P	0.9878	likely_pathogenic	0.9945	pathogenic	-1.435	Destabilizing	1.0	D	0.885	deleterious	D	0.557941538	None	None	N
L/Q	0.9401	likely_pathogenic	0.9655	pathogenic	-2.297	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
L/R	0.9548	likely_pathogenic	0.9719	pathogenic	-1.99	Destabilizing	1.0	D	0.882	deleterious	D	0.557941538	None	None	N
L/S	0.9746	likely_pathogenic	0.9865	pathogenic	-3.325	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
L/T	0.9307	likely_pathogenic	0.9576	pathogenic	-2.842	Highly Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
L/V	0.1504	likely_benign	0.2088	benign	-1.435	Destabilizing	0.767	D	0.405	neutral	N	0.520233815	None	None	N
L/W	0.7473	likely_pathogenic	0.8748	pathogenic	-1.998	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
L/Y	0.8251	likely_pathogenic	0.8997	pathogenic	-1.725	Destabilizing	1.0	D	0.827	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.