TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6407	19444;19445;19446	chr2:178728707;178728706;178728705	chr2:179593434;179593433;179593432
N2AB	6090	18493;18494;18495	chr2:178728707;178728706;178728705	chr2:179593434;179593433;179593432
N2A	5163	15712;15713;15714	chr2:178728707;178728706;178728705	chr2:179593434;179593433;179593432
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: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-48
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.2313
• 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	rs747444832	None	0.047	N	0.25	0.079	0.629781192331	gnomAD-4.0.0	7.52968E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.89826E-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	0.1678	likely_benign	0.141	benign	-1.607	Destabilizing	0.047	N	0.25	neutral	N	0.500925696	None	None	N
V/C	0.7796	likely_pathogenic	0.7508	pathogenic	-1.094	Destabilizing	0.94	D	0.509	neutral	None	None	None	None	N
V/D	0.4086	ambiguous	0.4187	ambiguous	-1.67	Destabilizing	0.351	N	0.557	neutral	N	0.497866748	None	None	N
V/E	0.2322	likely_benign	0.2224	benign	-1.668	Destabilizing	0.228	N	0.455	neutral	None	None	None	None	N
V/F	0.1698	likely_benign	0.1584	benign	-1.289	Destabilizing	0.487	N	0.559	neutral	N	0.507266532	None	None	N
V/G	0.3317	likely_benign	0.2958	benign	-1.929	Destabilizing	0.183	N	0.503	neutral	N	0.517762018	None	None	N
V/H	0.4732	ambiguous	0.4268	ambiguous	-1.504	Destabilizing	0.94	D	0.563	neutral	None	None	None	None	N
V/I	0.0759	likely_benign	0.0709	benign	-0.816	Destabilizing	0.101	N	0.351	neutral	N	0.502139204	None	None	N
V/K	0.2158	likely_benign	0.1869	benign	-1.378	Destabilizing	0.001	N	0.312	neutral	None	None	None	None	N
V/L	0.1861	likely_benign	0.1599	benign	-0.816	Destabilizing	0.001	N	0.222	neutral	N	0.478166267	None	None	N
V/M	0.1127	likely_benign	0.099	benign	-0.594	Destabilizing	0.716	D	0.465	neutral	None	None	None	None	N
V/N	0.2811	likely_benign	0.2443	benign	-1.202	Destabilizing	0.418	N	0.566	neutral	None	None	None	None	N
V/P	0.837	likely_pathogenic	0.8072	pathogenic	-1.046	Destabilizing	0.593	D	0.571	neutral	None	None	None	None	N
V/Q	0.2465	likely_benign	0.2138	benign	-1.387	Destabilizing	0.418	N	0.57	neutral	None	None	None	None	N
V/R	0.1953	likely_benign	0.1768	benign	-0.833	Destabilizing	0.002	N	0.423	neutral	None	None	None	None	N
V/S	0.2104	likely_benign	0.1762	benign	-1.698	Destabilizing	0.129	N	0.437	neutral	None	None	None	None	N
V/T	0.1149	likely_benign	0.0944	benign	-1.593	Destabilizing	0.001	N	0.163	neutral	None	None	None	None	N
V/W	0.7869	likely_pathogenic	0.7727	pathogenic	-1.508	Destabilizing	0.983	D	0.577	neutral	None	None	None	None	N
V/Y	0.5623	ambiguous	0.5265	ambiguous	-1.215	Destabilizing	0.836	D	0.563	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.