TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4905	14938;14939;14940	chr2:178735733;178735732;178735731	chr2:179600460;179600459;179600458
N2AB	4588	13987;13988;13989	chr2:178735733;178735732;178735731	chr2:179600460;179600459;179600458
N2A	3661	11206;11207;11208	chr2:178735733;178735732;178735731	chr2:179600460;179600459;179600458
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: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-32
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.2241
• 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
V/D	None	None	0.484	D	0.753	0.52	0.6731056941	gnomAD-4.0.0	7.20193E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.87501E-06	0	0
V/I	rs774495507	-0.633	None	N	0.153	0.074	0.15556083564	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.59E-05	None	0	None	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
V/A	0.3158	likely_benign	0.3186	benign	-2.031	Highly Destabilizing	0.052	N	0.508	neutral	N	0.353945372	None	None	N
V/C	0.7086	likely_pathogenic	0.7131	pathogenic	-1.671	Destabilizing	0.935	D	0.702	prob.neutral	None	None	None	None	N
V/D	0.8365	likely_pathogenic	0.8439	pathogenic	-2.343	Highly Destabilizing	0.484	N	0.753	deleterious	D	0.695579277	None	None	N
V/E	0.7791	likely_pathogenic	0.7836	pathogenic	-2.233	Highly Destabilizing	0.555	D	0.741	deleterious	None	None	None	None	N
V/F	0.2005	likely_benign	0.1962	benign	-1.305	Destabilizing	0.062	N	0.734	prob.delet.	N	0.514457695	None	None	N
V/G	0.4359	ambiguous	0.4509	ambiguous	-2.479	Highly Destabilizing	0.484	N	0.753	deleterious	D	0.595749891	None	None	N
V/H	0.8503	likely_pathogenic	0.8476	pathogenic	-2.044	Highly Destabilizing	0.935	D	0.701	prob.neutral	None	None	None	None	N
V/I	0.0617	likely_benign	0.0599	benign	-0.837	Destabilizing	None	N	0.153	neutral	N	0.449977633	None	None	N
V/K	0.8347	likely_pathogenic	0.8334	pathogenic	-1.95	Destabilizing	0.555	D	0.745	deleterious	None	None	None	None	N
V/L	0.1246	likely_benign	0.1207	benign	-0.837	Destabilizing	None	N	0.168	neutral	N	0.452808236	None	None	N
V/M	0.1517	likely_benign	0.1405	benign	-0.782	Destabilizing	0.38	N	0.664	neutral	None	None	None	None	N
V/N	0.6205	likely_pathogenic	0.62	pathogenic	-1.978	Destabilizing	0.791	D	0.755	deleterious	None	None	None	None	N
V/P	0.8693	likely_pathogenic	0.8774	pathogenic	-1.204	Destabilizing	0.791	D	0.738	prob.delet.	None	None	None	None	N
V/Q	0.7461	likely_pathogenic	0.7447	pathogenic	-2.004	Highly Destabilizing	0.791	D	0.722	prob.delet.	None	None	None	None	N
V/R	0.7722	likely_pathogenic	0.7707	pathogenic	-1.482	Destabilizing	0.555	D	0.757	deleterious	None	None	None	None	N
V/S	0.4768	ambiguous	0.479	ambiguous	-2.565	Highly Destabilizing	0.262	N	0.699	prob.neutral	None	None	None	None	N
V/T	0.3783	ambiguous	0.3718	ambiguous	-2.328	Highly Destabilizing	0.149	N	0.601	neutral	None	None	None	None	N
V/W	0.8465	likely_pathogenic	0.8399	pathogenic	-1.65	Destabilizing	0.935	D	0.701	prob.neutral	None	None	None	None	N
V/Y	0.6269	likely_pathogenic	0.6109	pathogenic	-1.35	Destabilizing	0.555	D	0.752	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.