TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5486	16681;16682;16683	chr2:178732605;178732604;178732603	chr2:179597332;179597331;179597330
N2AB	5169	15730;15731;15732	chr2:178732605;178732604;178732603	chr2:179597332;179597331;179597330
N2A	4242	12949;12950;12951	chr2:178732605;178732604;178732603	chr2:179597332;179597331;179597330
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: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-38
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.3576
• 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
G/D	None	None	0.003	N	0.32	0.128	0.0920862733494	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
G/S	rs1430669284	-0.391	0.338	N	0.492	0.298	0.159798565429	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
G/S	rs1430669284	-0.391	0.338	N	0.492	0.298	0.159798565429	gnomAD-4.0.0	1.36856E-06	None	None	None	None	N	None	0	2.23754E-05	None	0	0	None	0	0	8.99509E-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
G/A	0.1866	likely_benign	0.2017	benign	-0.408	Destabilizing	0.013	N	0.278	neutral	N	0.461910312	None	None	N
G/C	0.3482	ambiguous	0.3695	ambiguous	-0.84	Destabilizing	0.988	D	0.703	prob.neutral	N	0.502513369	None	None	N
G/D	0.0851	likely_benign	0.092	benign	-0.38	Destabilizing	0.003	N	0.32	neutral	N	0.415396427	None	None	N
G/E	0.1412	likely_benign	0.1439	benign	-0.496	Destabilizing	0.018	N	0.341	neutral	None	None	None	None	N
G/F	0.6865	likely_pathogenic	0.745	pathogenic	-0.882	Destabilizing	0.967	D	0.684	prob.neutral	None	None	None	None	N
G/H	0.4118	ambiguous	0.4525	ambiguous	-0.81	Destabilizing	0.991	D	0.649	neutral	None	None	None	None	N
G/I	0.532	ambiguous	0.589	pathogenic	-0.29	Destabilizing	0.906	D	0.683	prob.neutral	None	None	None	None	N
G/K	0.43	ambiguous	0.4855	ambiguous	-0.908	Destabilizing	0.575	D	0.597	neutral	None	None	None	None	N
G/L	0.533	ambiguous	0.5785	pathogenic	-0.29	Destabilizing	0.826	D	0.637	neutral	None	None	None	None	N
G/M	0.5841	likely_pathogenic	0.6359	pathogenic	-0.353	Destabilizing	0.991	D	0.677	prob.neutral	None	None	None	None	N
G/N	0.1581	likely_benign	0.1741	benign	-0.552	Destabilizing	0.704	D	0.495	neutral	None	None	None	None	N
G/P	0.9147	likely_pathogenic	0.9353	pathogenic	-0.29	Destabilizing	0.906	D	0.64	neutral	None	None	None	None	N
G/Q	0.2978	likely_benign	0.3209	benign	-0.764	Destabilizing	0.826	D	0.637	neutral	None	None	None	None	N
G/R	0.3512	ambiguous	0.4034	ambiguous	-0.573	Destabilizing	0.782	D	0.639	neutral	N	0.465455485	None	None	N
G/S	0.1364	likely_benign	0.142	benign	-0.808	Destabilizing	0.338	N	0.492	neutral	N	0.464695016	None	None	N
G/T	0.3424	ambiguous	0.3684	ambiguous	-0.838	Destabilizing	0.575	D	0.59	neutral	None	None	None	None	N
G/V	0.3676	ambiguous	0.4084	ambiguous	-0.29	Destabilizing	0.782	D	0.626	neutral	N	0.456670073	None	None	N
G/W	0.4934	ambiguous	0.5341	ambiguous	-1.124	Destabilizing	0.991	D	0.703	prob.neutral	None	None	None	None	N
G/Y	0.4406	ambiguous	0.5116	ambiguous	-0.735	Destabilizing	0.967	D	0.681	prob.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.