TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5791	17596;17597;17598	chr2:178731395;178731394;178731393	chr2:179596122;179596121;179596120
N2AB	5474	16645;16646;16647	chr2:178731395;178731394;178731393	chr2:179596122;179596121;179596120
N2A	4547	13864;13865;13866	chr2:178731395;178731394;178731393	chr2:179596122;179596121;179596120
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: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-41
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.2411
• 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
G/S	rs1276489578	-0.684	0.01	N	0.105	0.127	0.110078149338	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
G/S	rs1276489578	-0.684	0.01	N	0.105	0.127	0.110078149338	gnomAD-4.0.0	1.36839E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79892E-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
G/A	0.0958	likely_benign	0.0947	benign	-0.677	Destabilizing	0.002	N	0.109	neutral	N	0.409166675	None	None	N
G/C	0.2283	likely_benign	0.201	benign	-1.048	Destabilizing	0.98	D	0.465	neutral	N	0.491014481	None	None	N
G/D	0.1262	likely_benign	0.115	benign	-1.133	Destabilizing	0.002	N	0.148	neutral	N	0.382401362	None	None	N
G/E	0.1504	likely_benign	0.1407	benign	-1.265	Destabilizing	0.031	N	0.214	neutral	None	None	None	None	N
G/F	0.4869	ambiguous	0.4541	ambiguous	-1.354	Destabilizing	0.944	D	0.489	neutral	None	None	None	None	N
G/H	0.2244	likely_benign	0.2064	benign	-1.056	Destabilizing	0.981	D	0.453	neutral	None	None	None	None	N
G/I	0.2833	likely_benign	0.278	benign	-0.611	Destabilizing	0.893	D	0.483	neutral	None	None	None	None	N
G/K	0.204	likely_benign	0.185	benign	-1.12	Destabilizing	0.704	D	0.402	neutral	None	None	None	None	N
G/L	0.346	ambiguous	0.3222	benign	-0.611	Destabilizing	0.704	D	0.444	neutral	None	None	None	None	N
G/M	0.3884	ambiguous	0.3691	ambiguous	-0.43	Destabilizing	0.981	D	0.466	neutral	None	None	None	None	N
G/N	0.1478	likely_benign	0.1344	benign	-0.777	Destabilizing	0.704	D	0.328	neutral	None	None	None	None	N
G/P	0.8227	likely_pathogenic	0.7732	pathogenic	-0.597	Destabilizing	0.828	D	0.42	neutral	None	None	None	None	N
G/Q	0.1829	likely_benign	0.1689	benign	-1.089	Destabilizing	0.704	D	0.408	neutral	None	None	None	None	N
G/R	0.1404	likely_benign	0.1318	benign	-0.661	Destabilizing	0.642	D	0.444	neutral	N	0.410166753	None	None	N
G/S	0.0791	likely_benign	0.0823	benign	-0.963	Destabilizing	0.01	N	0.105	neutral	N	0.355985551	None	None	N
G/T	0.1262	likely_benign	0.1249	benign	-1.028	Destabilizing	0.031	N	0.226	neutral	None	None	None	None	N
G/V	0.1892	likely_benign	0.1884	benign	-0.597	Destabilizing	0.473	N	0.447	neutral	N	0.461211649	None	None	N
G/W	0.3694	ambiguous	0.357	ambiguous	-1.536	Destabilizing	0.995	D	0.462	neutral	None	None	None	None	N
G/Y	0.344	ambiguous	0.3257	benign	-1.178	Destabilizing	0.981	D	0.496	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.