TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7640	23143;23144;23145	chr2:178721101;178721100;178721099	chr2:179585828;179585827;179585826
N2AB	7323	22192;22193;22194	chr2:178721101;178721100;178721099	chr2:179585828;179585827;179585826
N2A	6396	19411;19412;19413	chr2:178721101;178721100;178721099	chr2:179585828;179585827;179585826
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-61
• Domain position: 33
• Structural Position: 46
• Q(SASA): 0.2553
• 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/I	rs1245374725	None	0.001	N	0.232	0.186	0.416454006429	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	2.625E-06	0	0
V/L	rs1245374725	-0.189	0.12	D	0.514	0.418	0.457013227636	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-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	0.5021	ambiguous	0.4836	ambiguous	-1.808	Destabilizing	0.637	D	0.683	prob.neutral	D	0.589408467	None	None	N
V/C	0.9489	likely_pathogenic	0.9405	pathogenic	-1.076	Destabilizing	0.998	D	0.716	prob.delet.	None	None	None	None	N
V/D	0.9652	likely_pathogenic	0.9716	pathogenic	-2.258	Highly Destabilizing	0.987	D	0.851	deleterious	D	0.61943807	None	None	N
V/E	0.9301	likely_pathogenic	0.9475	pathogenic	-2.082	Highly Destabilizing	0.941	D	0.818	deleterious	None	None	None	None	N
V/F	0.5051	ambiguous	0.5375	ambiguous	-1.123	Destabilizing	0.965	D	0.753	deleterious	D	0.540219922	None	None	N
V/G	0.6866	likely_pathogenic	0.6699	pathogenic	-2.291	Highly Destabilizing	0.99	D	0.823	deleterious	D	0.635457431	None	None	N
V/H	0.976	likely_pathogenic	0.9811	pathogenic	-2.007	Highly Destabilizing	0.998	D	0.83	deleterious	None	None	None	None	N
V/I	0.1003	likely_benign	0.1097	benign	-0.483	Destabilizing	0.001	N	0.232	neutral	N	0.467765633	None	None	N
V/K	0.9529	likely_pathogenic	0.9649	pathogenic	-1.487	Destabilizing	0.945	D	0.824	deleterious	None	None	None	None	N
V/L	0.4958	ambiguous	0.5555	ambiguous	-0.483	Destabilizing	0.12	N	0.514	neutral	D	0.543914914	None	None	N
V/M	0.4352	ambiguous	0.4528	ambiguous	-0.341	Destabilizing	0.963	D	0.641	neutral	None	None	None	None	N
V/N	0.9165	likely_pathogenic	0.9277	pathogenic	-1.638	Destabilizing	0.838	D	0.856	deleterious	None	None	None	None	N
V/P	0.8796	likely_pathogenic	0.9207	pathogenic	-0.896	Destabilizing	0.94	D	0.851	deleterious	None	None	None	None	N
V/Q	0.9404	likely_pathogenic	0.9526	pathogenic	-1.563	Destabilizing	0.987	D	0.843	deleterious	None	None	None	None	N
V/R	0.9376	likely_pathogenic	0.9515	pathogenic	-1.264	Destabilizing	0.987	D	0.851	deleterious	None	None	None	None	N
V/S	0.7884	likely_pathogenic	0.7762	pathogenic	-2.201	Highly Destabilizing	0.738	D	0.823	deleterious	None	None	None	None	N
V/T	0.5452	ambiguous	0.5258	ambiguous	-1.89	Destabilizing	0.03	N	0.389	neutral	None	None	None	None	N
V/W	0.9779	likely_pathogenic	0.9824	pathogenic	-1.605	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
V/Y	0.9032	likely_pathogenic	0.9186	pathogenic	-1.193	Destabilizing	0.996	D	0.733	prob.delet.	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.