TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21948	66067;66068;66069	chr2:178582961;178582960;178582959	chr2:179447688;179447687;179447686
N2AB	20307	61144;61145;61146	chr2:178582961;178582960;178582959	chr2:179447688;179447687;179447686
N2A	19380	58363;58364;58365	chr2:178582961;178582960;178582959	chr2:179447688;179447687;179447686
N2B	12883	38872;38873;38874	chr2:178582961;178582960;178582959	chr2:179447688;179447687;179447686
Novex-1	13008	39247;39248;39249	chr2:178582961;178582960;178582959	chr2:179447688;179447687;179447686
Novex-2	13075	39448;39449;39450	chr2:178582961;178582960;178582959	chr2:179447688;179447687;179447686
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-125
• Domain position: 83
• Structural Position: 171
• Q(SASA): 0.2631
• 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
T/A	None	None	0.835	N	0.58	0.259	0.317378411342	gnomAD-4.0.0	7.21209E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.31699E-07	0	0
T/S	None	None	0.489	N	0.335	0.212	0.212008924253	gnomAD-4.0.0	7.21209E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.31699E-07	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
T/A	0.0716	likely_benign	0.0713	benign	-0.573	Destabilizing	0.835	D	0.58	neutral	N	0.498157537	None	None	N
T/C	0.3196	likely_benign	0.2952	benign	-0.305	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
T/D	0.3578	ambiguous	0.3467	ambiguous	0.004	Stabilizing	0.942	D	0.657	neutral	None	None	None	None	N
T/E	0.3271	likely_benign	0.3124	benign	-0.057	Destabilizing	0.97	D	0.665	neutral	None	None	None	None	N
T/F	0.2314	likely_benign	0.24	benign	-0.954	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
T/G	0.2168	likely_benign	0.209	benign	-0.743	Destabilizing	0.97	D	0.753	deleterious	None	None	None	None	N
T/H	0.2132	likely_benign	0.1974	benign	-1.081	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
T/I	0.1347	likely_benign	0.1345	benign	-0.236	Destabilizing	0.994	D	0.745	deleterious	D	0.532867543	None	None	N
T/K	0.1976	likely_benign	0.1894	benign	-0.516	Destabilizing	0.97	D	0.666	neutral	None	None	None	None	N
T/L	0.11	likely_benign	0.1091	benign	-0.236	Destabilizing	0.985	D	0.669	neutral	None	None	None	None	N
T/M	0.0949	likely_benign	0.0961	benign	0.092	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
T/N	0.1021	likely_benign	0.0944	benign	-0.315	Destabilizing	0.248	N	0.288	neutral	N	0.485748387	None	None	N
T/P	0.2016	likely_benign	0.2003	benign	-0.318	Destabilizing	0.994	D	0.745	deleterious	N	0.518130164	None	None	N
T/Q	0.2034	likely_benign	0.1927	benign	-0.57	Destabilizing	0.996	D	0.749	deleterious	None	None	None	None	N
T/R	0.1788	likely_benign	0.1695	benign	-0.222	Destabilizing	0.996	D	0.739	prob.delet.	None	None	None	None	N
T/S	0.092	likely_benign	0.0898	benign	-0.556	Destabilizing	0.489	N	0.335	neutral	N	0.45232646	None	None	N
T/V	0.0977	likely_benign	0.0995	benign	-0.318	Destabilizing	0.985	D	0.568	neutral	None	None	None	None	N
T/W	0.6142	likely_pathogenic	0.616	pathogenic	-0.903	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
T/Y	0.2682	likely_benign	0.2662	benign	-0.65	Destabilizing	0.999	D	0.823	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.