TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9630	29113;29114;29115	chr2:178707679;178707678;178707677	chr2:179572406;179572405;179572404
N2AB	9313	28162;28163;28164	chr2:178707679;178707678;178707677	chr2:179572406;179572405;179572404
N2A	8386	25381;25382;25383	chr2:178707679;178707678;178707677	chr2:179572406;179572405;179572404
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: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-82
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.1915
• 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/T	None	None	0.062	None	0.476	0.413	0.628505682511	gnomAD-4.0.0	1.36834E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.31884E-05	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	0.7507	likely_pathogenic	0.6651	pathogenic	-2.362	Highly Destabilizing	0.035	N	0.438	neutral	None	None	None	None	N
I/C	0.8835	likely_pathogenic	0.838	pathogenic	-1.49	Destabilizing	0.824	D	0.53	neutral	None	None	None	None	N
I/D	0.9757	likely_pathogenic	0.9575	pathogenic	-2.765	Highly Destabilizing	0.555	D	0.603	neutral	None	None	None	None	N
I/E	0.9248	likely_pathogenic	0.8819	pathogenic	-2.543	Highly Destabilizing	0.555	D	0.594	neutral	None	None	None	None	N
I/F	0.3154	likely_benign	0.2493	benign	-1.474	Destabilizing	0.38	N	0.503	neutral	None	None	None	None	N
I/G	0.9177	likely_pathogenic	0.8633	pathogenic	-2.863	Highly Destabilizing	0.555	D	0.585	neutral	None	None	None	None	N
I/H	0.9274	likely_pathogenic	0.8794	pathogenic	-2.203	Highly Destabilizing	0.935	D	0.596	neutral	None	None	None	None	N
I/K	0.8774	likely_pathogenic	0.8067	pathogenic	-1.847	Destabilizing	0.317	N	0.587	neutral	None	None	None	None	N
I/L	0.1238	likely_benign	0.1127	benign	-0.914	Destabilizing	None	N	0.091	neutral	None	None	None	None	N
I/M	0.124	likely_benign	0.096	benign	-0.766	Destabilizing	0.004	N	0.297	neutral	None	None	None	None	N
I/N	0.8021	likely_pathogenic	0.7008	pathogenic	-2.19	Highly Destabilizing	0.555	D	0.61	neutral	None	None	None	None	N
I/P	0.9671	likely_pathogenic	0.9413	pathogenic	-1.38	Destabilizing	0.791	D	0.605	neutral	None	None	None	None	N
I/Q	0.868	likely_pathogenic	0.7867	pathogenic	-2.08	Highly Destabilizing	0.555	D	0.613	neutral	None	None	None	None	N
I/R	0.8352	likely_pathogenic	0.7342	pathogenic	-1.574	Destabilizing	0.317	N	0.606	neutral	None	None	None	None	N
I/S	0.8147	likely_pathogenic	0.7184	pathogenic	-2.809	Highly Destabilizing	0.149	N	0.515	neutral	None	None	None	None	N
I/T	0.7268	likely_pathogenic	0.6325	pathogenic	-2.442	Highly Destabilizing	0.062	N	0.476	neutral	None	None	None	None	N
I/V	0.0952	likely_benign	0.0866	benign	-1.38	Destabilizing	None	N	0.111	neutral	None	None	None	None	N
I/W	0.9119	likely_pathogenic	0.8595	pathogenic	-1.806	Destabilizing	0.935	D	0.617	neutral	None	None	None	None	N
I/Y	0.7703	likely_pathogenic	0.7009	pathogenic	-1.493	Destabilizing	0.555	D	0.559	neutral	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.