TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33149	99670;99671;99672	chr2:178537762;178537761;178537760	chr2:179402489;179402488;179402487
N2AB	31508	94747;94748;94749	chr2:178537762;178537761;178537760	chr2:179402489;179402488;179402487
N2A	30581	91966;91967;91968	chr2:178537762;178537761;178537760	chr2:179402489;179402488;179402487
N2B	24084	72475;72476;72477	chr2:178537762;178537761;178537760	chr2:179402489;179402488;179402487
Novex-1	24209	72850;72851;72852	chr2:178537762;178537761;178537760	chr2:179402489;179402488;179402487
Novex-2	24276	73051;73052;73053	chr2:178537762;178537761;178537760	chr2:179402489;179402488;179402487
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-156
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.1546
• 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
M/T	rs750670014	-0.312	0.026	N	0.303	0.329	0.729516068776	gnomAD-2.1.1	8.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
M/T	rs750670014	-0.312	0.026	N	0.303	0.329	0.729516068776	gnomAD-4.0.0	4.77404E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.29836E-05	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
M/A	0.7346	likely_pathogenic	0.8071	pathogenic	-1.803	Destabilizing	0.645	D	0.386	neutral	None	None	None	None	N
M/C	0.9036	likely_pathogenic	0.9153	pathogenic	-1.4	Destabilizing	0.999	D	0.472	neutral	None	None	None	None	N
M/D	0.9826	likely_pathogenic	0.9847	pathogenic	-0.33	Destabilizing	0.903	D	0.54	neutral	None	None	None	None	N
M/E	0.8954	likely_pathogenic	0.9186	pathogenic	-0.25	Destabilizing	0.516	D	0.486	neutral	None	None	None	None	N
M/F	0.4003	ambiguous	0.387	ambiguous	-0.707	Destabilizing	0.745	D	0.428	neutral	None	None	None	None	N
M/G	0.9207	likely_pathogenic	0.9459	pathogenic	-2.173	Highly Destabilizing	0.898	D	0.512	neutral	None	None	None	None	N
M/H	0.8756	likely_pathogenic	0.8933	pathogenic	-1.285	Destabilizing	0.997	D	0.521	neutral	None	None	None	None	N
M/I	0.4951	ambiguous	0.5874	pathogenic	-0.82	Destabilizing	0.551	D	0.378	neutral	N	0.395913029	None	None	N
M/K	0.6867	likely_pathogenic	0.7276	pathogenic	-0.445	Destabilizing	0.551	D	0.429	neutral	N	0.51770609	None	None	N
M/L	0.2325	likely_benign	0.2933	benign	-0.82	Destabilizing	0.1	N	0.234	neutral	N	0.453961255	None	None	N
M/N	0.8604	likely_pathogenic	0.8778	pathogenic	-0.422	Destabilizing	0.903	D	0.515	neutral	None	None	None	None	N
M/P	0.9704	likely_pathogenic	0.9757	pathogenic	-1.121	Destabilizing	0.949	D	0.524	neutral	None	None	None	None	N
M/Q	0.6184	likely_pathogenic	0.6547	pathogenic	-0.39	Destabilizing	0.963	D	0.43	neutral	None	None	None	None	N
M/R	0.7092	likely_pathogenic	0.7599	pathogenic	-0.168	Destabilizing	0.903	D	0.468	neutral	D	0.524613419	None	None	N
M/S	0.7974	likely_pathogenic	0.8369	pathogenic	-1.13	Destabilizing	0.815	D	0.391	neutral	None	None	None	None	N
M/T	0.5789	likely_pathogenic	0.6663	pathogenic	-0.917	Destabilizing	0.026	N	0.303	neutral	N	0.453174609	None	None	N
M/V	0.1958	likely_benign	0.2477	benign	-1.121	Destabilizing	0.363	N	0.373	neutral	N	0.411783772	None	None	N
M/W	0.861	likely_pathogenic	0.8895	pathogenic	-0.679	Destabilizing	0.999	D	0.489	neutral	None	None	None	None	N
M/Y	0.7707	likely_pathogenic	0.7976	pathogenic	-0.68	Destabilizing	0.991	D	0.48	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.