TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4824	14695;14696;14697	chr2:178735976;178735975;178735974	chr2:179600703;179600702;179600701
N2AB	4507	13744;13745;13746	chr2:178735976;178735975;178735974	chr2:179600703;179600702;179600701
N2A	3580	10963;10964;10965	chr2:178735976;178735975;178735974	chr2:179600703;179600702;179600701
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-31
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.1689
• 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
I/T	None	None	0.959	D	0.569	0.4	0.75913351157	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
I/V	rs772792515	-1.411	0.509	D	0.361	0.31	0.627389779515	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	5.58E-05	None	0	None	0	0	0
I/V	rs772792515	-1.411	0.509	D	0.361	0.31	0.627389779515	gnomAD-4.0.0	1.5913E-06	None	None	None	None	I	None	0	0	None	0	2.77423E-05	None	0	0	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
I/A	0.3784	ambiguous	0.3403	ambiguous	-2.0	Highly Destabilizing	0.863	D	0.522	neutral	None	None	None	None	I
I/C	0.8945	likely_pathogenic	0.8714	pathogenic	-1.229	Destabilizing	0.999	D	0.596	neutral	None	None	None	None	I
I/D	0.9644	likely_pathogenic	0.9565	pathogenic	-2.026	Highly Destabilizing	0.997	D	0.673	neutral	None	None	None	None	I
I/E	0.8954	likely_pathogenic	0.8854	pathogenic	-2.017	Highly Destabilizing	0.997	D	0.673	neutral	None	None	None	None	I
I/F	0.4294	ambiguous	0.3738	ambiguous	-1.558	Destabilizing	0.939	D	0.575	neutral	None	None	None	None	I
I/G	0.8535	likely_pathogenic	0.8293	pathogenic	-2.339	Highly Destabilizing	0.991	D	0.677	prob.neutral	None	None	None	None	I
I/H	0.9045	likely_pathogenic	0.8861	pathogenic	-1.699	Destabilizing	0.999	D	0.623	neutral	None	None	None	None	I
I/K	0.7811	likely_pathogenic	0.7687	pathogenic	-1.375	Destabilizing	0.988	D	0.683	prob.neutral	D	0.727542817	None	None	I
I/L	0.2222	likely_benign	0.1877	benign	-1.116	Destabilizing	0.015	N	0.107	neutral	D	0.664222765	None	None	I
I/M	0.1387	likely_benign	0.1183	benign	-0.821	Destabilizing	0.31	N	0.21	neutral	D	0.690124005	None	None	I
I/N	0.7335	likely_pathogenic	0.7041	pathogenic	-1.212	Destabilizing	0.997	D	0.685	prob.neutral	None	None	None	None	I
I/P	0.6328	likely_pathogenic	0.6351	pathogenic	-1.383	Destabilizing	0.997	D	0.683	prob.neutral	None	None	None	None	I
I/Q	0.8095	likely_pathogenic	0.7877	pathogenic	-1.431	Destabilizing	0.991	D	0.685	prob.neutral	None	None	None	None	I
I/R	0.6777	likely_pathogenic	0.6548	pathogenic	-0.785	Destabilizing	0.988	D	0.673	neutral	D	0.785699315	None	None	I
I/S	0.5449	ambiguous	0.5147	ambiguous	-1.754	Destabilizing	0.969	D	0.614	neutral	None	None	None	None	I
I/T	0.2048	likely_benign	0.1844	benign	-1.636	Destabilizing	0.959	D	0.569	neutral	D	0.643467047	None	None	I
I/V	0.1171	likely_benign	0.1091	benign	-1.383	Destabilizing	0.509	D	0.361	neutral	D	0.666091924	None	None	I
I/W	0.9415	likely_pathogenic	0.9212	pathogenic	-1.688	Destabilizing	0.999	D	0.627	neutral	None	None	None	None	I
I/Y	0.8786	likely_pathogenic	0.8452	pathogenic	-1.459	Destabilizing	0.997	D	0.649	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.