TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7589	22990;22991;22992	chr2:178721898;178721897;178721896	chr2:179586625;179586624;179586623
N2AB	7272	22039;22040;22041	chr2:178721898;178721897;178721896	chr2:179586625;179586624;179586623
N2A	6345	19258;19259;19260	chr2:178721898;178721897;178721896	chr2:179586625;179586624;179586623
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: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-60
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.0841
• 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/V	None	None	0.976	N	0.349	0.407	0.584736501517	gnomAD-4.0.0	1.5928E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86103E-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
A/C	0.9342	likely_pathogenic	0.9234	pathogenic	-1.546	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
A/D	0.9977	likely_pathogenic	0.997	pathogenic	-2.913	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
A/E	0.9944	likely_pathogenic	0.9933	pathogenic	-2.729	Highly Destabilizing	1.0	D	0.821	deleterious	D	0.65690766	None	None	N
A/F	0.9536	likely_pathogenic	0.9453	pathogenic	-0.68	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
A/G	0.4912	ambiguous	0.4881	ambiguous	-1.81	Destabilizing	0.998	D	0.626	neutral	D	0.603307986	None	None	N
A/H	0.9978	likely_pathogenic	0.9972	pathogenic	-1.991	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
A/I	0.6466	likely_pathogenic	0.6341	pathogenic	-0.238	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
A/K	0.9989	likely_pathogenic	0.9986	pathogenic	-1.397	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
A/L	0.666	likely_pathogenic	0.6925	pathogenic	-0.238	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
A/M	0.8181	likely_pathogenic	0.8178	pathogenic	-0.612	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
A/N	0.9934	likely_pathogenic	0.9923	pathogenic	-1.754	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
A/P	0.9963	likely_pathogenic	0.9954	pathogenic	-0.584	Destabilizing	1.0	D	0.856	deleterious	D	0.631369549	None	None	N
A/Q	0.9924	likely_pathogenic	0.9915	pathogenic	-1.573	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
A/R	0.9956	likely_pathogenic	0.9947	pathogenic	-1.396	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
A/S	0.5603	ambiguous	0.5528	ambiguous	-2.082	Highly Destabilizing	0.992	D	0.637	neutral	D	0.603106182	None	None	N
A/T	0.6564	likely_pathogenic	0.6716	pathogenic	-1.798	Destabilizing	0.998	D	0.651	neutral	D	0.630764136	None	None	N
A/V	0.3032	likely_benign	0.3104	benign	-0.584	Destabilizing	0.976	D	0.349	neutral	N	0.505974128	None	None	N
A/W	0.9985	likely_pathogenic	0.9981	pathogenic	-1.433	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
A/Y	0.9899	likely_pathogenic	0.9874	pathogenic	-1.012	Destabilizing	1.0	D	0.892	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.