TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5452	16579;16580;16581	chr2:178732707;178732706;178732705	chr2:179597434;179597433;179597432
N2AB	5135	15628;15629;15630	chr2:178732707;178732706;178732705	chr2:179597434;179597433;179597432
N2A	4208	12847;12848;12849	chr2:178732707;178732706;178732705	chr2:179597434;179597433;179597432
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: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-38
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.133
• 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/V	None	None	1.0	N	0.772	0.666	0.869393105286	gnomAD-4.0.0	1.64863E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.12617E-05

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	0.9618	likely_pathogenic	0.9712	pathogenic	-2.74	Highly Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
F/C	0.9369	likely_pathogenic	0.9466	pathogenic	-1.712	Destabilizing	1.0	D	0.849	deleterious	D	0.556541138	None	None	N
F/D	0.9955	likely_pathogenic	0.9965	pathogenic	-2.181	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
F/E	0.995	likely_pathogenic	0.9962	pathogenic	-2.022	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
F/G	0.9906	likely_pathogenic	0.9921	pathogenic	-3.139	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
F/H	0.9778	likely_pathogenic	0.9817	pathogenic	-1.463	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
F/I	0.6132	likely_pathogenic	0.6714	pathogenic	-1.473	Destabilizing	1.0	D	0.773	deleterious	N	0.49746689	None	None	N
F/K	0.9967	likely_pathogenic	0.9975	pathogenic	-1.64	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
F/L	0.9676	likely_pathogenic	0.9754	pathogenic	-1.473	Destabilizing	0.999	D	0.679	prob.neutral	N	0.503363554	None	None	N
F/M	0.8756	likely_pathogenic	0.8967	pathogenic	-1.255	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
F/N	0.9877	likely_pathogenic	0.9893	pathogenic	-1.853	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
F/P	0.9944	likely_pathogenic	0.9948	pathogenic	-1.9	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
F/Q	0.9936	likely_pathogenic	0.9949	pathogenic	-1.902	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
F/R	0.9902	likely_pathogenic	0.9922	pathogenic	-1.048	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
F/S	0.9637	likely_pathogenic	0.9721	pathogenic	-2.66	Highly Destabilizing	1.0	D	0.857	deleterious	D	0.556034159	None	None	N
F/T	0.967	likely_pathogenic	0.9782	pathogenic	-2.4	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
F/V	0.6647	likely_pathogenic	0.7236	pathogenic	-1.9	Destabilizing	1.0	D	0.772	deleterious	N	0.498323898	None	None	N
F/W	0.8757	likely_pathogenic	0.8896	pathogenic	-0.409	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
F/Y	0.6506	likely_pathogenic	0.6717	pathogenic	-0.729	Destabilizing	0.999	D	0.624	neutral	D	0.556287649	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.