TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27344	82255;82256;82257	chr2:178564102;178564101;178564100	chr2:179428829;179428828;179428827
N2AB	25703	77332;77333;77334	chr2:178564102;178564101;178564100	chr2:179428829;179428828;179428827
N2A	24776	74551;74552;74553	chr2:178564102;178564101;178564100	chr2:179428829;179428828;179428827
N2B	18279	55060;55061;55062	chr2:178564102;178564101;178564100	chr2:179428829;179428828;179428827
Novex-1	18404	55435;55436;55437	chr2:178564102;178564101;178564100	chr2:179428829;179428828;179428827
Novex-2	18471	55636;55637;55638	chr2:178564102;178564101;178564100	chr2:179428829;179428828;179428827
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-140
• Domain position: 67
• Structural Position: 151
• Q(SASA): 0.2796
• 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
G/R	None	None	1.0	N	0.904	0.38	0.633221168995	gnomAD-4.0.0	2.05265E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69852E-06	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	0.1272	likely_benign	0.1403	benign	-0.573	Destabilizing	0.999	D	0.538	neutral	N	0.467466483	None	None	I
G/C	0.2734	likely_benign	0.2794	benign	-0.979	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
G/D	0.7099	likely_pathogenic	0.7341	pathogenic	-0.568	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
G/E	0.5831	likely_pathogenic	0.6222	pathogenic	-0.59	Destabilizing	1.0	D	0.875	deleterious	N	0.496767883	None	None	I
G/F	0.8594	likely_pathogenic	0.8694	pathogenic	-0.86	Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	I
G/H	0.6928	likely_pathogenic	0.7132	pathogenic	-1.203	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	I
G/I	0.6035	likely_pathogenic	0.6464	pathogenic	-0.076	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	I
G/K	0.6957	likely_pathogenic	0.7414	pathogenic	-0.983	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	I
G/L	0.7235	likely_pathogenic	0.7523	pathogenic	-0.076	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	I
G/M	0.6657	likely_pathogenic	0.6774	pathogenic	-0.207	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	I
G/N	0.5894	likely_pathogenic	0.5897	pathogenic	-0.761	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
G/P	0.9865	likely_pathogenic	0.987	pathogenic	-0.198	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	I
G/Q	0.5712	likely_pathogenic	0.6017	pathogenic	-0.835	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	I
G/R	0.4945	ambiguous	0.5577	ambiguous	-0.83	Destabilizing	1.0	D	0.904	deleterious	N	0.515799148	None	None	I
G/S	0.0853	likely_benign	0.0876	benign	-1.147	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	I
G/T	0.1556	likely_benign	0.1532	benign	-1.056	Destabilizing	0.991	D	0.577	neutral	None	None	None	None	I
G/V	0.4475	ambiguous	0.4865	ambiguous	-0.198	Destabilizing	1.0	D	0.873	deleterious	N	0.481564953	None	None	I
G/W	0.778	likely_pathogenic	0.801	pathogenic	-1.249	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	I
G/Y	0.7622	likely_pathogenic	0.7796	pathogenic	-0.773	Destabilizing	1.0	D	0.897	deleterious	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.