TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3416	10471;10472;10473	chr2:178759041;178759040;178759039	chr2:179623768;179623767;179623766
N2AB	3416	10471;10472;10473	chr2:178759041;178759040;178759039	chr2:179623768;179623767;179623766
N2A	3416	10471;10472;10473	chr2:178759041;178759040;178759039	chr2:179623768;179623767;179623766
N2B	3370	10333;10334;10335	chr2:178759041;178759040;178759039	chr2:179623768;179623767;179623766
Novex-1	3370	10333;10334;10335	chr2:178759041;178759040;178759039	chr2:179623768;179623767;179623766
Novex-2	3370	10333;10334;10335	chr2:178759041;178759040;178759039	chr2:179623768;179623767;179623766
Novex-3	3416	10471;10472;10473	chr2:178759041;178759040;178759039	chr2:179623768;179623767;179623766

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-24
• Domain position: 72
• Structural Position: 156
• Q(SASA): 0.0779
• 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
F/L	None	None	0.826	N	0.671	0.416	0.543254643676	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
F/A	0.9409	likely_pathogenic	0.9323	pathogenic	-2.214	Highly Destabilizing	0.863	D	0.763	deleterious	None	None	None	None	N
F/C	0.5971	likely_pathogenic	0.5572	ambiguous	-0.954	Destabilizing	0.015	N	0.579	neutral	N	0.213780176	None	None	N
F/D	0.9997	likely_pathogenic	0.9995	pathogenic	-2.89	Highly Destabilizing	0.997	D	0.84	deleterious	None	None	None	None	N
F/E	0.9994	likely_pathogenic	0.9992	pathogenic	-2.638	Highly Destabilizing	0.997	D	0.852	deleterious	None	None	None	None	N
F/G	0.9908	likely_pathogenic	0.9894	pathogenic	-2.683	Highly Destabilizing	0.969	D	0.798	deleterious	None	None	None	None	N
F/H	0.9951	likely_pathogenic	0.9931	pathogenic	-1.803	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
F/I	0.6229	likely_pathogenic	0.5813	pathogenic	-0.674	Destabilizing	0.959	D	0.687	prob.neutral	N	0.409485256	None	None	N
F/K	0.9995	likely_pathogenic	0.9993	pathogenic	-1.471	Destabilizing	0.997	D	0.839	deleterious	None	None	None	None	N
F/L	0.9427	likely_pathogenic	0.9431	pathogenic	-0.674	Destabilizing	0.826	D	0.671	neutral	N	0.457263496	None	None	N
F/M	0.8299	likely_pathogenic	0.811	pathogenic	-0.438	Destabilizing	0.997	D	0.687	prob.neutral	None	None	None	None	N
F/N	0.9981	likely_pathogenic	0.9974	pathogenic	-2.134	Highly Destabilizing	0.997	D	0.855	deleterious	None	None	None	None	N
F/P	0.9998	likely_pathogenic	0.9997	pathogenic	-1.201	Destabilizing	0.997	D	0.854	deleterious	None	None	None	None	N
F/Q	0.9985	likely_pathogenic	0.9981	pathogenic	-1.905	Destabilizing	0.997	D	0.861	deleterious	None	None	None	None	N
F/R	0.9972	likely_pathogenic	0.9965	pathogenic	-1.479	Destabilizing	0.997	D	0.855	deleterious	None	None	None	None	N
F/S	0.9852	likely_pathogenic	0.9794	pathogenic	-2.591	Highly Destabilizing	0.959	D	0.761	deleterious	N	0.512669473	None	None	N
F/T	0.9814	likely_pathogenic	0.9771	pathogenic	-2.213	Highly Destabilizing	0.969	D	0.776	deleterious	None	None	None	None	N
F/V	0.4917	ambiguous	0.469	ambiguous	-1.201	Destabilizing	0.92	D	0.727	prob.delet.	N	0.350412847	None	None	N
F/W	0.9644	likely_pathogenic	0.9412	pathogenic	-0.018	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	N
F/Y	0.7363	likely_pathogenic	0.6404	pathogenic	-0.385	Destabilizing	0.986	D	0.629	neutral	N	0.512154872	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.