TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5664	17215;17216;17217	chr2:178731885;178731884;178731883	chr2:179596612;179596611;179596610
N2AB	5347	16264;16265;16266	chr2:178731885;178731884;178731883	chr2:179596612;179596611;179596610
N2A	4420	13483;13484;13485	chr2:178731885;178731884;178731883	chr2:179596612;179596611;179596610
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: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-40
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.3773
• Predicted PPI site: I

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
P/L	None	None	0.379	D	0.431	0.504	0.73019596334	gnomAD-4.0.0	1.59139E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85856E-06	0	0
P/S	None	None	0.045	N	0.213	0.327	0.252681307341	gnomAD-4.0.0	6.84239E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99504E-07	0	0
P/T	None	None	0.004	D	0.215	0.397	0.393316636838	gnomAD-4.0.0	2.05272E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69851E-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
P/A	0.0752	likely_benign	0.0862	benign	-0.543	Destabilizing	0.002	N	0.171	neutral	N	0.497648609	None	None	I
P/C	0.5392	ambiguous	0.6921	pathogenic	-0.506	Destabilizing	0.992	D	0.53	neutral	None	None	None	None	I
P/D	0.5735	likely_pathogenic	0.692	pathogenic	-0.616	Destabilizing	0.617	D	0.502	neutral	None	None	None	None	I
P/E	0.2958	likely_benign	0.3863	ambiguous	-0.701	Destabilizing	0.617	D	0.519	neutral	None	None	None	None	I
P/F	0.4675	ambiguous	0.6298	pathogenic	-0.72	Destabilizing	0.92	D	0.548	neutral	None	None	None	None	I
P/G	0.3975	ambiguous	0.4352	ambiguous	-0.692	Destabilizing	0.447	N	0.429	neutral	None	None	None	None	I
P/H	0.2141	likely_benign	0.314	benign	-0.246	Destabilizing	0.99	D	0.49	neutral	D	0.561863031	None	None	I
P/I	0.2891	likely_benign	0.46	ambiguous	-0.279	Destabilizing	0.739	D	0.583	neutral	None	None	None	None	I
P/K	0.3074	likely_benign	0.4231	ambiguous	-0.516	Destabilizing	0.617	D	0.519	neutral	None	None	None	None	I
P/L	0.1139	likely_benign	0.1825	benign	-0.279	Destabilizing	0.379	N	0.431	neutral	D	0.561863031	None	None	I
P/M	0.2784	likely_benign	0.4102	ambiguous	-0.453	Destabilizing	0.25	N	0.335	neutral	None	None	None	None	I
P/N	0.4149	ambiguous	0.5596	ambiguous	-0.222	Destabilizing	0.85	D	0.53	neutral	None	None	None	None	I
P/Q	0.154	likely_benign	0.2214	benign	-0.443	Destabilizing	0.92	D	0.496	neutral	None	None	None	None	I
P/R	0.193	likely_benign	0.2777	benign	-0.021	Destabilizing	0.81	D	0.531	neutral	D	0.561459423	None	None	I
P/S	0.1152	likely_benign	0.1511	benign	-0.519	Destabilizing	0.045	N	0.213	neutral	N	0.507623651	None	None	I
P/T	0.117	likely_benign	0.1722	benign	-0.508	Destabilizing	0.004	N	0.215	neutral	D	0.561459423	None	None	I
P/V	0.1978	likely_benign	0.305	benign	-0.334	Destabilizing	0.447	N	0.471	neutral	None	None	None	None	I
P/W	0.709	likely_pathogenic	0.8248	pathogenic	-0.829	Destabilizing	0.992	D	0.582	neutral	None	None	None	None	I
P/Y	0.4451	ambiguous	0.6	pathogenic	-0.528	Destabilizing	0.972	D	0.551	neutral	None	None	None	None	I

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.