TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23655	71188;71189;71190	chr2:178575169;178575168;178575167	chr2:179439896;179439895;179439894
N2AB	22014	66265;66266;66267	chr2:178575169;178575168;178575167	chr2:179439896;179439895;179439894
N2A	21087	63484;63485;63486	chr2:178575169;178575168;178575167	chr2:179439896;179439895;179439894
N2B	14590	43993;43994;43995	chr2:178575169;178575168;178575167	chr2:179439896;179439895;179439894
Novex-1	14715	44368;44369;44370	chr2:178575169;178575168;178575167	chr2:179439896;179439895;179439894
Novex-2	14782	44569;44570;44571	chr2:178575169;178575168;178575167	chr2:179439896;179439895;179439894
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-130
• Domain position: 19
• Structural Position: 33
• Q(SASA): 0.0631
• 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	rs794729488	None	1.0	N	0.835	0.445	0.586935410679	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
I/T	rs794729488	None	1.0	N	0.835	0.445	0.586935410679	gnomAD-4.0.0	1.30221E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.78064E-05	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	0.9515	likely_pathogenic	0.9617	pathogenic	-1.828	Destabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	N
I/C	0.9491	likely_pathogenic	0.9584	pathogenic	-1.398	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
I/D	0.9979	likely_pathogenic	0.9984	pathogenic	-1.097	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
I/E	0.9963	likely_pathogenic	0.9973	pathogenic	-1.008	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
I/F	0.5724	likely_pathogenic	0.6258	pathogenic	-1.086	Destabilizing	1.0	D	0.817	deleterious	N	0.462364385	None	None	N
I/G	0.9899	likely_pathogenic	0.9923	pathogenic	-2.219	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
I/H	0.9913	likely_pathogenic	0.9935	pathogenic	-1.185	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
I/K	0.9905	likely_pathogenic	0.9928	pathogenic	-1.331	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
I/L	0.2795	likely_benign	0.3242	benign	-0.788	Destabilizing	0.993	D	0.459	neutral	N	0.507386656	None	None	N
I/M	0.3501	ambiguous	0.4083	ambiguous	-0.824	Destabilizing	1.0	D	0.771	deleterious	N	0.467390814	None	None	N
I/N	0.9638	likely_pathogenic	0.9717	pathogenic	-1.39	Destabilizing	1.0	D	0.9	deleterious	N	0.485748559	None	None	N
I/P	0.9957	likely_pathogenic	0.9966	pathogenic	-1.106	Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
I/Q	0.9929	likely_pathogenic	0.9948	pathogenic	-1.413	Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
I/R	0.9888	likely_pathogenic	0.9915	pathogenic	-0.826	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
I/S	0.9664	likely_pathogenic	0.9734	pathogenic	-2.1	Highly Destabilizing	1.0	D	0.865	deleterious	N	0.462364385	None	None	N
I/T	0.9605	likely_pathogenic	0.971	pathogenic	-1.867	Destabilizing	1.0	D	0.835	deleterious	N	0.461857406	None	None	N
I/V	0.1511	likely_benign	0.171	benign	-1.106	Destabilizing	0.993	D	0.415	neutral	N	0.422189114	None	None	N
I/W	0.9896	likely_pathogenic	0.9914	pathogenic	-1.148	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
I/Y	0.9373	likely_pathogenic	0.9506	pathogenic	-0.938	Destabilizing	1.0	D	0.833	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.