TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6457	19594;19595;19596	chr2:178728557;178728556;178728555	chr2:179593284;179593283;179593282
N2AB	6140	18643;18644;18645	chr2:178728557;178728556;178728555	chr2:179593284;179593283;179593282
N2A	5213	15862;15863;15864	chr2:178728557;178728556;178728555	chr2:179593284;179593283;179593282
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: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-48
• Domain position: 73
• Structural Position: 156
• Q(SASA): 0.069
• 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/I	None	None	0.961	N	0.735	0.213	0.382761230579	gnomAD-4.0.0	1.59309E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8608E-06	0	0
F/L	rs2079784971	None	0.135	N	0.437	0.113	0.260735089382	gnomAD-4.0.0	1.59322E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86103E-06	0	0
F/S	rs2079785463	None	0.997	N	0.815	0.546	0.42748209135	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.966	likely_pathogenic	0.9496	pathogenic	-2.799	Highly Destabilizing	0.985	D	0.794	deleterious	None	None	None	None	N
F/C	0.6353	likely_pathogenic	0.4727	ambiguous	-1.529	Destabilizing	0.265	N	0.709	prob.delet.	N	0.35078951	None	None	N
F/D	0.9997	likely_pathogenic	0.9994	pathogenic	-3.243	Highly Destabilizing	0.999	D	0.864	deleterious	None	None	None	None	N
F/E	0.9991	likely_pathogenic	0.9987	pathogenic	-3.035	Highly Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
F/G	0.9919	likely_pathogenic	0.9872	pathogenic	-3.234	Highly Destabilizing	0.998	D	0.845	deleterious	None	None	None	None	N
F/H	0.9955	likely_pathogenic	0.9923	pathogenic	-1.835	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
F/I	0.6851	likely_pathogenic	0.5518	ambiguous	-1.372	Destabilizing	0.961	D	0.735	prob.delet.	N	0.477831753	None	None	N
F/K	0.9992	likely_pathogenic	0.9988	pathogenic	-1.892	Destabilizing	0.999	D	0.862	deleterious	None	None	None	None	N
F/L	0.9514	likely_pathogenic	0.9293	pathogenic	-1.372	Destabilizing	0.135	N	0.437	neutral	N	0.454858893	None	None	N
F/M	0.7971	likely_pathogenic	0.7347	pathogenic	-1.021	Destabilizing	0.996	D	0.715	prob.delet.	None	None	None	None	N
F/N	0.9977	likely_pathogenic	0.9959	pathogenic	-2.399	Highly Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
F/P	0.9998	likely_pathogenic	0.9996	pathogenic	-1.86	Destabilizing	0.999	D	0.874	deleterious	None	None	None	None	N
F/Q	0.9976	likely_pathogenic	0.9965	pathogenic	-2.347	Highly Destabilizing	0.999	D	0.881	deleterious	None	None	None	None	N
F/R	0.9963	likely_pathogenic	0.9948	pathogenic	-1.461	Destabilizing	0.999	D	0.863	deleterious	None	None	None	None	N
F/S	0.9895	likely_pathogenic	0.9788	pathogenic	-2.983	Highly Destabilizing	0.997	D	0.815	deleterious	N	0.480695676	None	None	N
F/T	0.9898	likely_pathogenic	0.9823	pathogenic	-2.666	Highly Destabilizing	0.998	D	0.815	deleterious	None	None	None	None	N
F/V	0.5522	ambiguous	0.4206	ambiguous	-1.86	Destabilizing	0.961	D	0.771	deleterious	N	0.471751143	None	None	N
F/W	0.9667	likely_pathogenic	0.9499	pathogenic	-0.424	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
F/Y	0.7303	likely_pathogenic	0.6491	pathogenic	-0.804	Destabilizing	0.997	D	0.663	neutral	N	0.480695676	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.