TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20723	62392;62393;62394	chr2:178589558;178589557;178589556	chr2:179454285;179454284;179454283
N2AB	19082	57469;57470;57471	chr2:178589558;178589557;178589556	chr2:179454285;179454284;179454283
N2A	18155	54688;54689;54690	chr2:178589558;178589557;178589556	chr2:179454285;179454284;179454283
N2B	11658	35197;35198;35199	chr2:178589558;178589557;178589556	chr2:179454285;179454284;179454283
Novex-1	11783	35572;35573;35574	chr2:178589558;178589557;178589556	chr2:179454285;179454284;179454283
Novex-2	11850	35773;35774;35775	chr2:178589558;178589557;178589556	chr2:179454285;179454284;179454283
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-38
• Domain position: 56
• Structural Position: 77
• Q(SASA): 0.0823
• 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
I/T	rs779251870	-2.561	0.98	N	0.648	0.372	0.589254406313	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.65E-05	0	0
I/T	rs779251870	-2.561	0.98	N	0.648	0.372	0.589254406313	gnomAD-4.0.0	1.59205E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88338E-05	0	0	0	0
I/V	None	None	0.689	N	0.365	0.106	0.471052466308	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
I/A	0.8857	likely_pathogenic	0.9178	pathogenic	-2.452	Highly Destabilizing	0.965	D	0.579	neutral	None	None	None	None	N
I/C	0.9106	likely_pathogenic	0.9335	pathogenic	-1.561	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
I/D	0.9908	likely_pathogenic	0.992	pathogenic	-2.911	Highly Destabilizing	0.999	D	0.75	deleterious	None	None	None	None	N
I/E	0.9723	likely_pathogenic	0.9739	pathogenic	-2.683	Highly Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
I/F	0.6283	likely_pathogenic	0.6722	pathogenic	-1.472	Destabilizing	0.989	D	0.644	neutral	N	0.508475239	None	None	N
I/G	0.9808	likely_pathogenic	0.9855	pathogenic	-2.99	Highly Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
I/H	0.9683	likely_pathogenic	0.9762	pathogenic	-2.575	Highly Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
I/K	0.938	likely_pathogenic	0.9522	pathogenic	-1.776	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
I/L	0.2034	likely_benign	0.2428	benign	-0.887	Destabilizing	0.011	N	0.206	neutral	N	0.458777137	None	None	N
I/M	0.2765	likely_benign	0.3471	ambiguous	-0.752	Destabilizing	0.989	D	0.694	prob.neutral	N	0.473241662	None	None	N
I/N	0.9062	likely_pathogenic	0.9206	pathogenic	-2.099	Highly Destabilizing	0.998	D	0.767	deleterious	N	0.511416757	None	None	N
I/P	0.9695	likely_pathogenic	0.9681	pathogenic	-1.392	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
I/Q	0.9426	likely_pathogenic	0.9501	pathogenic	-1.959	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
I/R	0.9224	likely_pathogenic	0.9359	pathogenic	-1.563	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
I/S	0.905	likely_pathogenic	0.9202	pathogenic	-2.737	Highly Destabilizing	0.998	D	0.683	prob.neutral	N	0.487539819	None	None	N
I/T	0.8734	likely_pathogenic	0.8965	pathogenic	-2.369	Highly Destabilizing	0.98	D	0.648	neutral	N	0.500143757	None	None	N
I/V	0.1193	likely_benign	0.1539	benign	-1.392	Destabilizing	0.689	D	0.365	neutral	N	0.443482398	None	None	N
I/W	0.9717	likely_pathogenic	0.9765	pathogenic	-1.943	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
I/Y	0.9438	likely_pathogenic	0.9513	pathogenic	-1.636	Destabilizing	0.999	D	0.721	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.