TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33160	99703;99704;99705	chr2:178537729;178537728;178537727	chr2:179402456;179402455;179402454
N2AB	31519	94780;94781;94782	chr2:178537729;178537728;178537727	chr2:179402456;179402455;179402454
N2A	30592	91999;92000;92001	chr2:178537729;178537728;178537727	chr2:179402456;179402455;179402454
N2B	24095	72508;72509;72510	chr2:178537729;178537728;178537727	chr2:179402456;179402455;179402454
Novex-1	24220	72883;72884;72885	chr2:178537729;178537728;178537727	chr2:179402456;179402455;179402454
Novex-2	24287	73084;73085;73086	chr2:178537729;178537728;178537727	chr2:179402456;179402455;179402454
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-156
• Domain position: 60
• Structural Position: 140
• Q(SASA): 0.0934
• 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	rs794729553	None	0.023	N	0.272	0.077	0.286081765059	gnomAD-4.0.0	2.73691E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59789E-06	0	0
V/L	None	None	0.175	N	0.549	0.138	0.538283067721	gnomAD-4.0.0	2.73691E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59789E-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	0.818	likely_pathogenic	0.8575	pathogenic	-2.378	Highly Destabilizing	0.95	D	0.641	neutral	N	0.505788955	None	None	N
V/C	0.9489	likely_pathogenic	0.9579	pathogenic	-2.077	Highly Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
V/D	0.9949	likely_pathogenic	0.9967	pathogenic	-3.437	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
V/E	0.9845	likely_pathogenic	0.9892	pathogenic	-3.136	Highly Destabilizing	1.0	D	0.879	deleterious	N	0.518070314	None	None	N
V/F	0.5426	ambiguous	0.6521	pathogenic	-1.323	Destabilizing	0.994	D	0.815	deleterious	None	None	None	None	N
V/G	0.9337	likely_pathogenic	0.9564	pathogenic	-2.995	Highly Destabilizing	0.998	D	0.886	deleterious	N	0.518070314	None	None	N
V/H	0.9925	likely_pathogenic	0.9949	pathogenic	-2.893	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
V/I	0.0776	likely_benign	0.0781	benign	-0.596	Destabilizing	0.023	N	0.272	neutral	N	0.355628553	None	None	N
V/K	0.9877	likely_pathogenic	0.9902	pathogenic	-2.025	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
V/L	0.3428	ambiguous	0.408	ambiguous	-0.596	Destabilizing	0.175	N	0.549	neutral	N	0.414885579	None	None	N
V/M	0.3722	ambiguous	0.461	ambiguous	-0.864	Destabilizing	0.992	D	0.717	prob.delet.	None	None	None	None	N
V/N	0.9822	likely_pathogenic	0.9884	pathogenic	-2.639	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
V/P	0.9933	likely_pathogenic	0.9951	pathogenic	-1.169	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
V/Q	0.9825	likely_pathogenic	0.987	pathogenic	-2.323	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
V/R	0.981	likely_pathogenic	0.9848	pathogenic	-2.04	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
V/S	0.9556	likely_pathogenic	0.9675	pathogenic	-3.205	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
V/T	0.8981	likely_pathogenic	0.9137	pathogenic	-2.743	Highly Destabilizing	0.997	D	0.742	deleterious	None	None	None	None	N
V/W	0.9909	likely_pathogenic	0.9953	pathogenic	-1.959	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
V/Y	0.9635	likely_pathogenic	0.9772	pathogenic	-1.61	Destabilizing	1.0	D	0.805	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.