TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9347	28264;28265;28266	chr2:178711197;178711196;178711195	chr2:179575924;179575923;179575922
N2AB	9030	27313;27314;27315	chr2:178711197;178711196;178711195	chr2:179575924;179575923;179575922
N2A	8103	24532;24533;24534	chr2:178711197;178711196;178711195	chr2:179575924;179575923;179575922
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: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-79
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.147
• 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/A	None	None	0.012	None	0.491	0.196	0.438383285633	gnomAD-4.0.0	1.5911E-06	None	None	None	None	N	None	0	0	None	4.76644E-05	0	None	0	0	0	0	0
V/L	rs1382932532	-0.298	0.004	None	0.37	0.075	0.18995819373	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
V/L	rs1382932532	-0.298	0.004	None	0.37	0.075	0.18995819373	gnomAD-4.0.0	1.59109E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85812E-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
V/A	0.2539	likely_benign	0.3236	benign	-2.036	Highly Destabilizing	0.012	N	0.491	neutral	None	None	None	None	N
V/C	0.7023	likely_pathogenic	0.7146	pathogenic	-1.574	Destabilizing	0.864	D	0.628	neutral	None	None	None	None	N
V/D	0.5407	ambiguous	0.6871	pathogenic	-2.327	Highly Destabilizing	0.214	N	0.692	prob.neutral	None	None	None	None	N
V/E	0.3738	ambiguous	0.4869	ambiguous	-2.16	Highly Destabilizing	0.055	N	0.637	neutral	None	None	None	None	N
V/F	0.1122	likely_benign	0.1381	benign	-1.292	Destabilizing	None	N	0.459	neutral	None	None	None	None	N
V/G	0.3141	likely_benign	0.4103	ambiguous	-2.538	Highly Destabilizing	0.055	N	0.66	neutral	None	None	None	None	N
V/H	0.5551	ambiguous	0.6415	pathogenic	-2.238	Highly Destabilizing	0.001	N	0.571	neutral	None	None	None	None	N
V/I	0.0648	likely_benign	0.0654	benign	-0.665	Destabilizing	None	N	0.186	neutral	None	None	None	None	N
V/K	0.4735	ambiguous	0.5873	pathogenic	-1.682	Destabilizing	0.072	N	0.64	neutral	None	None	None	None	N
V/L	0.1234	likely_benign	0.1433	benign	-0.665	Destabilizing	0.004	N	0.37	neutral	None	None	None	None	N
V/M	0.1098	likely_benign	0.1273	benign	-0.631	Destabilizing	0.214	N	0.633	neutral	None	None	None	None	N
V/N	0.3959	ambiguous	0.4963	ambiguous	-1.836	Destabilizing	0.214	N	0.688	prob.neutral	None	None	None	None	N
V/P	0.9124	likely_pathogenic	0.9574	pathogenic	-1.092	Destabilizing	0.356	N	0.651	neutral	None	None	None	None	N
V/Q	0.382	ambiguous	0.4754	ambiguous	-1.76	Destabilizing	0.356	N	0.659	neutral	None	None	None	None	N
V/R	0.3851	ambiguous	0.4799	ambiguous	-1.419	Destabilizing	0.356	N	0.676	prob.neutral	None	None	None	None	N
V/S	0.2865	likely_benign	0.3657	ambiguous	-2.486	Highly Destabilizing	0.038	N	0.616	neutral	None	None	None	None	N
V/T	0.1976	likely_benign	0.2291	benign	-2.18	Highly Destabilizing	0.001	N	0.277	neutral	None	None	None	None	N
V/W	0.6333	likely_pathogenic	0.7381	pathogenic	-1.744	Destabilizing	0.676	D	0.65	neutral	None	None	None	None	N
V/Y	0.3744	ambiguous	0.4486	ambiguous	-1.386	Destabilizing	0.001	N	0.455	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.