TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3262	10009;10010;10011	chr2:178764731;178764730;178764729	chr2:179629458;179629457;179629456
N2AB	3262	10009;10010;10011	chr2:178764731;178764730;178764729	chr2:179629458;179629457;179629456
N2A	3262	10009;10010;10011	chr2:178764731;178764730;178764729	chr2:179629458;179629457;179629456
N2B	3216	9871;9872;9873	chr2:178764731;178764730;178764729	chr2:179629458;179629457;179629456
Novex-1	3216	9871;9872;9873	chr2:178764731;178764730;178764729	chr2:179629458;179629457;179629456
Novex-2	3216	9871;9872;9873	chr2:178764731;178764730;178764729	chr2:179629458;179629457;179629456
Novex-3	3262	10009;10010;10011	chr2:178764731;178764730;178764729	chr2:179629458;179629457;179629456

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-23
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1217
• 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
I/L	None	None	0.19	N	0.393	0.222	0.54988173901	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25001E-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
I/A	0.9206	likely_pathogenic	0.9625	pathogenic	-2.713	Highly Destabilizing	0.415	N	0.685	prob.neutral	None	None	None	None	N
I/C	0.9501	likely_pathogenic	0.9746	pathogenic	-1.881	Destabilizing	0.989	D	0.782	deleterious	None	None	None	None	N
I/D	0.9985	likely_pathogenic	0.9995	pathogenic	-3.149	Highly Destabilizing	0.987	D	0.837	deleterious	None	None	None	None	N
I/E	0.996	likely_pathogenic	0.9986	pathogenic	-2.91	Highly Destabilizing	0.961	D	0.827	deleterious	None	None	None	None	N
I/F	0.3078	likely_benign	0.4313	ambiguous	-1.564	Destabilizing	0.923	D	0.761	deleterious	None	None	None	None	N
I/G	0.9907	likely_pathogenic	0.9966	pathogenic	-3.254	Highly Destabilizing	0.961	D	0.803	deleterious	None	None	None	None	N
I/H	0.9884	likely_pathogenic	0.9962	pathogenic	-2.671	Highly Destabilizing	0.996	D	0.833	deleterious	None	None	None	None	N
I/K	0.9917	likely_pathogenic	0.997	pathogenic	-2.137	Highly Destabilizing	0.949	D	0.829	deleterious	D	0.622164337	None	None	N
I/L	0.2412	likely_benign	0.3496	ambiguous	-1.131	Destabilizing	0.19	N	0.393	neutral	N	0.501056338	None	None	N
I/M	0.313	likely_benign	0.4244	ambiguous	-1.102	Destabilizing	0.901	D	0.717	prob.delet.	D	0.62041965	None	None	N
I/N	0.9796	likely_pathogenic	0.9938	pathogenic	-2.524	Highly Destabilizing	0.987	D	0.837	deleterious	None	None	None	None	N
I/P	0.9949	likely_pathogenic	0.998	pathogenic	-1.642	Destabilizing	0.987	D	0.835	deleterious	None	None	None	None	N
I/Q	0.9902	likely_pathogenic	0.9963	pathogenic	-2.368	Highly Destabilizing	0.987	D	0.833	deleterious	None	None	None	None	N
I/R	0.985	likely_pathogenic	0.9941	pathogenic	-1.821	Destabilizing	0.949	D	0.835	deleterious	D	0.622164337	None	None	N
I/S	0.9614	likely_pathogenic	0.9855	pathogenic	-3.176	Highly Destabilizing	0.923	D	0.782	deleterious	None	None	None	None	N
I/T	0.9013	likely_pathogenic	0.961	pathogenic	-2.802	Highly Destabilizing	0.722	D	0.715	prob.delet.	N	0.518838759	None	None	N
I/V	0.1031	likely_benign	0.12	benign	-1.642	Destabilizing	0.001	N	0.249	neutral	N	0.35973028	None	None	N
I/W	0.9823	likely_pathogenic	0.9926	pathogenic	-1.987	Destabilizing	0.996	D	0.827	deleterious	None	None	None	None	N
I/Y	0.9269	likely_pathogenic	0.9649	pathogenic	-1.725	Destabilizing	0.961	D	0.795	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.