TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7133	21622;21623;21624	chr2:178723862;178723861;178723860	chr2:179588589;179588588;179588587
N2AB	6816	20671;20672;20673	chr2:178723862;178723861;178723860	chr2:179588589;179588588;179588587
N2A	5889	17890;17891;17892	chr2:178723862;178723861;178723860	chr2:179588589;179588588;179588587
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-55
• Domain position: 90
• Structural Position: 177
• Q(SASA): 0.4497
• 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	rs2078874176	None	0.645	D	0.545	0.622	0.787508662514	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/A	rs2078874176	None	0.645	D	0.545	0.622	0.787508662514	gnomAD-4.0.0	1.8687E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.5557E-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	0.533	ambiguous	0.4916	ambiguous	-1.685	Destabilizing	0.645	D	0.545	neutral	D	0.653575198	None	None	N
V/C	0.9356	likely_pathogenic	0.9247	pathogenic	-1.233	Destabilizing	0.995	D	0.629	neutral	None	None	None	None	N
V/D	0.9653	likely_pathogenic	0.9481	pathogenic	-1.564	Destabilizing	0.945	D	0.693	prob.neutral	None	None	None	None	N
V/E	0.9014	likely_pathogenic	0.8737	pathogenic	-1.537	Destabilizing	0.928	D	0.653	neutral	D	0.65418061	None	None	N
V/F	0.4706	ambiguous	0.4348	ambiguous	-1.264	Destabilizing	0.894	D	0.621	neutral	None	None	None	None	N
V/G	0.7297	likely_pathogenic	0.6696	pathogenic	-2.031	Highly Destabilizing	0.928	D	0.668	neutral	D	0.65418061	None	None	N
V/H	0.9665	likely_pathogenic	0.9563	pathogenic	-1.53	Destabilizing	0.995	D	0.689	prob.neutral	None	None	None	None	N
V/I	0.0761	likely_benign	0.0752	benign	-0.815	Destabilizing	0.006	N	0.467	neutral	N	0.519082088	None	None	N
V/K	0.9177	likely_pathogenic	0.8898	pathogenic	-1.272	Destabilizing	0.945	D	0.651	neutral	None	None	None	None	N
V/L	0.2977	likely_benign	0.2843	benign	-0.815	Destabilizing	0.006	N	0.455	neutral	D	0.593748157	None	None	N
V/M	0.3005	likely_benign	0.2879	benign	-0.698	Destabilizing	0.894	D	0.635	neutral	None	None	None	None	N
V/N	0.887	likely_pathogenic	0.8514	pathogenic	-1.118	Destabilizing	0.981	D	0.695	prob.neutral	None	None	None	None	N
V/P	0.8583	likely_pathogenic	0.8243	pathogenic	-1.072	Destabilizing	0.981	D	0.659	neutral	None	None	None	None	N
V/Q	0.9004	likely_pathogenic	0.8682	pathogenic	-1.279	Destabilizing	0.981	D	0.662	neutral	None	None	None	None	N
V/R	0.877	likely_pathogenic	0.8348	pathogenic	-0.81	Destabilizing	0.945	D	0.694	prob.neutral	None	None	None	None	N
V/S	0.7487	likely_pathogenic	0.7001	pathogenic	-1.705	Destabilizing	0.945	D	0.624	neutral	None	None	None	None	N
V/T	0.6316	likely_pathogenic	0.59	pathogenic	-1.567	Destabilizing	0.707	D	0.607	neutral	None	None	None	None	N
V/W	0.9734	likely_pathogenic	0.9669	pathogenic	-1.455	Destabilizing	0.995	D	0.663	neutral	None	None	None	None	N
V/Y	0.9178	likely_pathogenic	0.8999	pathogenic	-1.163	Destabilizing	0.945	D	0.62	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.