TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33379	100360;100361;100362	chr2:178536974;178536973;178536972	chr2:179401701;179401700;179401699
N2AB	31738	95437;95438;95439	chr2:178536974;178536973;178536972	chr2:179401701;179401700;179401699
N2A	30811	92656;92657;92658	chr2:178536974;178536973;178536972	chr2:179401701;179401700;179401699
N2B	24314	73165;73166;73167	chr2:178536974;178536973;178536972	chr2:179401701;179401700;179401699
Novex-1	24439	73540;73541;73542	chr2:178536974;178536973;178536972	chr2:179401701;179401700;179401699
Novex-2	24506	73741;73742;73743	chr2:178536974;178536973;178536972	chr2:179401701;179401700;179401699
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-130
• Domain position: 90
• Structural Position: 122
• Q(SASA): 0.4461
• 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
E/G	None	None	0.999	N	0.754	0.458	0.437420747294	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
E/K	None	None	0.997	N	0.835	0.416	0.344251166708	gnomAD-4.0.0	6.84462E-07	None	None	None	None	N	None	0	0	None	0	2.52232E-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
E/A	0.2949	likely_benign	0.2905	benign	-0.137	Destabilizing	0.997	D	0.817	deleterious	N	0.509088527	None	None	N
E/C	0.9339	likely_pathogenic	0.9314	pathogenic	-0.089	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
E/D	0.3753	ambiguous	0.3965	ambiguous	-0.934	Destabilizing	0.997	D	0.772	deleterious	N	0.509261886	None	None	N
E/F	0.9014	likely_pathogenic	0.9058	pathogenic	0.788	Stabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
E/G	0.5405	ambiguous	0.5316	ambiguous	-0.566	Destabilizing	0.999	D	0.754	deleterious	N	0.469683263	None	None	N
E/H	0.7838	likely_pathogenic	0.7911	pathogenic	0.64	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
E/I	0.5256	ambiguous	0.5427	ambiguous	1.047	Stabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
E/K	0.4304	ambiguous	0.3736	ambiguous	-0.082	Destabilizing	0.997	D	0.835	deleterious	N	0.504298783	None	None	N
E/L	0.5992	likely_pathogenic	0.617	pathogenic	1.047	Stabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
E/M	0.6506	likely_pathogenic	0.655	pathogenic	1.275	Stabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
E/N	0.5873	likely_pathogenic	0.6216	pathogenic	-0.841	Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
E/P	0.817	likely_pathogenic	0.8558	pathogenic	0.676	Stabilizing	0.999	D	0.79	deleterious	None	None	None	None	N
E/Q	0.2824	likely_benign	0.2819	benign	-0.602	Destabilizing	0.999	D	0.804	deleterious	N	0.506800371	None	None	N
E/R	0.6084	likely_pathogenic	0.569	pathogenic	0.212	Stabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
E/S	0.4354	ambiguous	0.4627	ambiguous	-1.153	Destabilizing	0.998	D	0.823	deleterious	None	None	None	None	N
E/T	0.3762	ambiguous	0.3983	ambiguous	-0.771	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
E/V	0.3018	likely_benign	0.3153	benign	0.676	Stabilizing	0.999	D	0.794	deleterious	D	0.523231261	None	None	N
E/W	0.9781	likely_pathogenic	0.9788	pathogenic	1.018	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/Y	0.8722	likely_pathogenic	0.8775	pathogenic	1.086	Stabilizing	1.0	D	0.857	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.