TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7713	23362;23363;23364	chr2:178720625;178720624;178720623	chr2:179585352;179585351;179585350
N2AB	7396	22411;22412;22413	chr2:178720625;178720624;178720623	chr2:179585352;179585351;179585350
N2A	6469	19630;19631;19632	chr2:178720625;178720624;178720623	chr2:179585352;179585351;179585350
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: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-62
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.2144
• 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
A/T	rs778331160	-0.887	None	N	0.158	0.281	0.223146558224	gnomAD-2.1.1	1.24E-05	None	None	None	None	N	None	0	0	None	0	0	None	6.91E-05	None	0	9.06E-06	0
A/T	rs778331160	-0.887	None	N	0.158	0.281	0.223146558224	gnomAD-4.0.0	4.82194E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87753E-06	2.931E-05	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
A/C	0.4134	ambiguous	0.4553	ambiguous	-0.772	Destabilizing	0.356	N	0.542	neutral	None	None	None	None	N
A/D	0.5417	ambiguous	0.6095	pathogenic	-0.6	Destabilizing	0.029	N	0.568	neutral	N	0.507398798	None	None	N
A/E	0.4472	ambiguous	0.512	ambiguous	-0.545	Destabilizing	0.038	N	0.554	neutral	None	None	None	None	N
A/F	0.3236	likely_benign	0.3793	ambiguous	-0.587	Destabilizing	0.356	N	0.627	neutral	None	None	None	None	N
A/G	0.1509	likely_benign	0.1661	benign	-1.012	Destabilizing	None	N	0.138	neutral	N	0.467722773	None	None	N
A/H	0.6222	likely_pathogenic	0.6976	pathogenic	-1.291	Destabilizing	0.356	N	0.595	neutral	None	None	None	None	N
A/I	0.1871	likely_benign	0.2185	benign	0.179	Stabilizing	0.038	N	0.496	neutral	None	None	None	None	N
A/K	0.6509	likely_pathogenic	0.7204	pathogenic	-0.819	Destabilizing	0.038	N	0.555	neutral	None	None	None	None	N
A/L	0.1978	likely_benign	0.2429	benign	0.179	Stabilizing	0.016	N	0.485	neutral	None	None	None	None	N
A/M	0.2126	likely_benign	0.2557	benign	-0.002	Destabilizing	0.356	N	0.609	neutral	None	None	None	None	N
A/N	0.396	ambiguous	0.4627	ambiguous	-0.693	Destabilizing	0.038	N	0.605	neutral	None	None	None	None	N
A/P	0.6148	likely_pathogenic	0.6902	pathogenic	-0.055	Destabilizing	0.055	N	0.638	neutral	N	0.495789003	None	None	N
A/Q	0.4988	ambiguous	0.5665	pathogenic	-0.663	Destabilizing	0.214	N	0.637	neutral	None	None	None	None	N
A/R	0.5966	likely_pathogenic	0.6687	pathogenic	-0.795	Destabilizing	0.214	N	0.652	neutral	None	None	None	None	N
A/S	0.114	likely_benign	0.1222	benign	-1.186	Destabilizing	None	N	0.149	neutral	D	0.532195539	None	None	N
A/T	0.0827	likely_benign	0.0912	benign	-1.001	Destabilizing	None	N	0.158	neutral	N	0.482209436	None	None	N
A/V	0.1041	likely_benign	0.1177	benign	-0.055	Destabilizing	None	N	0.154	neutral	N	0.394448805	None	None	N
A/W	0.8056	likely_pathogenic	0.8591	pathogenic	-1.068	Destabilizing	0.864	D	0.611	neutral	None	None	None	None	N
A/Y	0.5255	ambiguous	0.5995	pathogenic	-0.55	Destabilizing	0.356	N	0.638	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.