TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26954	81085;81086;81087	chr2:178565272;178565271;178565270	chr2:179429999;179429998;179429997
N2AB	25313	76162;76163;76164	chr2:178565272;178565271;178565270	chr2:179429999;179429998;179429997
N2A	24386	73381;73382;73383	chr2:178565272;178565271;178565270	chr2:179429999;179429998;179429997
N2B	17889	53890;53891;53892	chr2:178565272;178565271;178565270	chr2:179429999;179429998;179429997
Novex-1	18014	54265;54266;54267	chr2:178565272;178565271;178565270	chr2:179429999;179429998;179429997
Novex-2	18081	54466;54467;54468	chr2:178565272;178565271;178565270	chr2:179429999;179429998;179429997
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-139
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.1326
• 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	None	None	0.892	D	0.651	0.662	0.589131389434	gnomAD-4.0.0	4.77479E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71785E-06	0	3.02499E-05

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	0.6437	likely_pathogenic	0.6183	pathogenic	-1.83	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
A/D	0.9963	likely_pathogenic	0.9949	pathogenic	-3.046	Highly Destabilizing	0.996	D	0.806	deleterious	None	None	None	None	N
A/E	0.9885	likely_pathogenic	0.9852	pathogenic	-2.955	Highly Destabilizing	0.983	D	0.785	deleterious	D	0.634155524	None	None	N
A/F	0.8746	likely_pathogenic	0.868	pathogenic	-0.933	Destabilizing	0.975	D	0.797	deleterious	None	None	None	None	N
A/G	0.322	likely_benign	0.2951	benign	-1.435	Destabilizing	0.944	D	0.631	neutral	D	0.564304325	None	None	N
A/H	0.9941	likely_pathogenic	0.9924	pathogenic	-1.464	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
A/I	0.3966	ambiguous	0.3666	ambiguous	-0.302	Destabilizing	0.845	D	0.683	prob.neutral	None	None	None	None	N
A/K	0.9955	likely_pathogenic	0.9942	pathogenic	-1.371	Destabilizing	0.987	D	0.783	deleterious	None	None	None	None	N
A/L	0.3835	ambiguous	0.3608	ambiguous	-0.302	Destabilizing	0.033	N	0.453	neutral	None	None	None	None	N
A/M	0.5521	ambiguous	0.5374	ambiguous	-0.705	Destabilizing	0.975	D	0.78	deleterious	None	None	None	None	N
A/N	0.9848	likely_pathogenic	0.98	pathogenic	-1.675	Destabilizing	0.996	D	0.793	deleterious	None	None	None	None	N
A/P	0.9936	likely_pathogenic	0.9908	pathogenic	-0.535	Destabilizing	0.994	D	0.791	deleterious	D	0.634155524	None	None	N
A/Q	0.9779	likely_pathogenic	0.9731	pathogenic	-1.729	Destabilizing	0.996	D	0.775	deleterious	None	None	None	None	N
A/R	0.9886	likely_pathogenic	0.986	pathogenic	-1.163	Destabilizing	0.987	D	0.784	deleterious	None	None	None	None	N
A/S	0.423	ambiguous	0.3837	ambiguous	-1.918	Destabilizing	0.944	D	0.625	neutral	D	0.601481029	None	None	N
A/T	0.3825	ambiguous	0.3356	benign	-1.737	Destabilizing	0.892	D	0.651	neutral	D	0.617298586	None	None	N
A/V	0.1827	likely_benign	0.1656	benign	-0.535	Destabilizing	0.025	N	0.385	neutral	N	0.513095278	None	None	N
A/W	0.9939	likely_pathogenic	0.9933	pathogenic	-1.474	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
A/Y	0.9712	likely_pathogenic	0.9686	pathogenic	-1.021	Destabilizing	0.987	D	0.801	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.