TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6193	18802;18803;18804	chr2:178729676;178729675;178729674	chr2:179594403;179594402;179594401
N2AB	5876	17851;17852;17853	chr2:178729676;178729675;178729674	chr2:179594403;179594402;179594401
N2A	4949	15070;15071;15072	chr2:178729676;178729675;178729674	chr2:179594403;179594402;179594401
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: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-45
• Domain position: 89
• Structural Position: 174
• Q(SASA): 0.1268
• 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
L/F	rs778348811	-1.617	0.997	D	0.815	0.531	0.631438196984	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	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
L/A	0.7632	likely_pathogenic	0.7864	pathogenic	-2.783	Highly Destabilizing	0.966	D	0.679	prob.neutral	None	None	None	None	N
L/C	0.83	likely_pathogenic	0.8285	pathogenic	-2.278	Highly Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
L/D	0.9914	likely_pathogenic	0.9941	pathogenic	-2.976	Highly Destabilizing	0.999	D	0.883	deleterious	None	None	None	None	N
L/E	0.9416	likely_pathogenic	0.9582	pathogenic	-2.661	Highly Destabilizing	0.998	D	0.875	deleterious	None	None	None	None	N
L/F	0.4174	ambiguous	0.4298	ambiguous	-1.648	Destabilizing	0.997	D	0.815	deleterious	D	0.629790809	None	None	N
L/G	0.9183	likely_pathogenic	0.9345	pathogenic	-3.422	Highly Destabilizing	0.998	D	0.881	deleterious	None	None	None	None	N
L/H	0.9204	likely_pathogenic	0.9363	pathogenic	-2.945	Highly Destabilizing	1.0	D	0.869	deleterious	D	0.656539746	None	None	N
L/I	0.1112	likely_benign	0.117	benign	-0.884	Destabilizing	0.955	D	0.634	neutral	D	0.570458458	None	None	N
L/K	0.9364	likely_pathogenic	0.9508	pathogenic	-2.095	Highly Destabilizing	0.998	D	0.872	deleterious	None	None	None	None	N
L/M	0.1661	likely_benign	0.1746	benign	-1.095	Destabilizing	0.998	D	0.787	deleterious	None	None	None	None	N
L/N	0.9532	likely_pathogenic	0.961	pathogenic	-2.674	Highly Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
L/P	0.9705	likely_pathogenic	0.9824	pathogenic	-1.504	Destabilizing	0.999	D	0.877	deleterious	D	0.656539746	None	None	N
L/Q	0.8313	likely_pathogenic	0.8696	pathogenic	-2.356	Highly Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
L/R	0.8909	likely_pathogenic	0.916	pathogenic	-2.086	Highly Destabilizing	0.999	D	0.881	deleterious	D	0.640520385	None	None	N
L/S	0.9275	likely_pathogenic	0.9393	pathogenic	-3.438	Highly Destabilizing	0.998	D	0.865	deleterious	None	None	None	None	N
L/T	0.7857	likely_pathogenic	0.8108	pathogenic	-2.94	Highly Destabilizing	0.995	D	0.815	deleterious	None	None	None	None	N
L/V	0.1122	likely_benign	0.118	benign	-1.504	Destabilizing	0.117	N	0.378	neutral	D	0.542978311	None	None	N
L/W	0.7846	likely_pathogenic	0.8164	pathogenic	-1.965	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
L/Y	0.8378	likely_pathogenic	0.8558	pathogenic	-1.73	Destabilizing	0.999	D	0.839	deleterious	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.