TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27379	82360;82361;82362	chr2:178563997;178563996;178563995	chr2:179428724;179428723;179428722
N2AB	25738	77437;77438;77439	chr2:178563997;178563996;178563995	chr2:179428724;179428723;179428722
N2A	24811	74656;74657;74658	chr2:178563997;178563996;178563995	chr2:179428724;179428723;179428722
N2B	18314	55165;55166;55167	chr2:178563997;178563996;178563995	chr2:179428724;179428723;179428722
Novex-1	18439	55540;55541;55542	chr2:178563997;178563996;178563995	chr2:179428724;179428723;179428722
Novex-2	18506	55741;55742;55743	chr2:178563997;178563996;178563995	chr2:179428724;179428723;179428722
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: Fn3-87
• Domain position: 11
• Structural Position: 12
• Q(SASA): 0.2636
• 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/L	None	None	0.898	N	0.481	0.23	0.379193981924	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.473	ambiguous	0.4433	ambiguous	-1.48	Destabilizing	0.977	D	0.557	neutral	D	0.523695407	None	None	N
V/C	0.8203	likely_pathogenic	0.8246	pathogenic	-1.178	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
V/D	0.9242	likely_pathogenic	0.907	pathogenic	-0.838	Destabilizing	0.999	D	0.874	deleterious	D	0.524816766	None	None	N
V/E	0.8617	likely_pathogenic	0.8417	pathogenic	-0.758	Destabilizing	0.999	D	0.873	deleterious	None	None	None	None	N
V/F	0.3549	ambiguous	0.3524	ambiguous	-0.944	Destabilizing	0.993	D	0.846	deleterious	N	0.489257547	None	None	N
V/G	0.642	likely_pathogenic	0.5931	pathogenic	-1.887	Destabilizing	0.999	D	0.867	deleterious	N	0.508825651	None	None	N
V/H	0.9424	likely_pathogenic	0.9395	pathogenic	-1.397	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/I	0.0743	likely_benign	0.077	benign	-0.438	Destabilizing	0.117	N	0.303	neutral	N	0.469941067	None	None	N
V/K	0.9095	likely_pathogenic	0.905	pathogenic	-1.154	Destabilizing	0.998	D	0.875	deleterious	None	None	None	None	N
V/L	0.3645	ambiguous	0.3664	ambiguous	-0.438	Destabilizing	0.898	D	0.481	neutral	N	0.518868378	None	None	N
V/M	0.3012	likely_benign	0.3028	benign	-0.472	Destabilizing	0.995	D	0.778	deleterious	None	None	None	None	N
V/N	0.8189	likely_pathogenic	0.7997	pathogenic	-1.089	Destabilizing	0.999	D	0.879	deleterious	None	None	None	None	N
V/P	0.7243	likely_pathogenic	0.7051	pathogenic	-0.75	Destabilizing	0.999	D	0.879	deleterious	None	None	None	None	N
V/Q	0.8774	likely_pathogenic	0.8687	pathogenic	-1.086	Destabilizing	0.999	D	0.881	deleterious	None	None	None	None	N
V/R	0.8894	likely_pathogenic	0.8789	pathogenic	-0.858	Destabilizing	0.999	D	0.878	deleterious	None	None	None	None	N
V/S	0.7112	likely_pathogenic	0.6776	pathogenic	-1.778	Destabilizing	0.998	D	0.871	deleterious	None	None	None	None	N
V/T	0.5947	likely_pathogenic	0.5703	pathogenic	-1.553	Destabilizing	0.983	D	0.689	prob.neutral	None	None	None	None	N
V/W	0.9434	likely_pathogenic	0.9473	pathogenic	-1.173	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
V/Y	0.8033	likely_pathogenic	0.7897	pathogenic	-0.842	Destabilizing	0.999	D	0.849	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.