TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35357	106294;106295;106296	chr2:178530546;178530545;178530544	chr2:179395273;179395272;179395271
N2AB	33716	101371;101372;101373	chr2:178530546;178530545;178530544	chr2:179395273;179395272;179395271
N2A	32789	98590;98591;98592	chr2:178530546;178530545;178530544	chr2:179395273;179395272;179395271
N2B	26292	79099;79100;79101	chr2:178530546;178530545;178530544	chr2:179395273;179395272;179395271
Novex-1	26417	79474;79475;79476	chr2:178530546;178530545;178530544	chr2:179395273;179395272;179395271
Novex-2	26484	79675;79676;79677	chr2:178530546;178530545;178530544	chr2:179395273;179395272;179395271
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-165
• Domain position: 72
• Structural Position: 154
• Q(SASA): 0.0783
• 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
Y/H	rs1649011462	None	1.0	D	0.785	0.887	0.720476626281	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
Y/H	rs1649011462	None	1.0	D	0.785	0.887	0.720476626281	gnomAD-4.0.0	6.57047E-06	None	None	None	None	N	None	0	6.54536E-05	None	0	0	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
Y/A	0.9958	likely_pathogenic	0.9945	pathogenic	-2.144	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
Y/C	0.9817	likely_pathogenic	0.9722	pathogenic	-1.479	Destabilizing	1.0	D	0.88	deleterious	D	0.65897745	None	None	N
Y/D	0.995	likely_pathogenic	0.9946	pathogenic	-3.035	Highly Destabilizing	1.0	D	0.878	deleterious	D	0.658775646	None	None	N
Y/E	0.9984	likely_pathogenic	0.9981	pathogenic	-2.792	Highly Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
Y/F	0.3191	likely_benign	0.2882	benign	-0.819	Destabilizing	0.999	D	0.678	prob.neutral	D	0.594042787	None	None	N
Y/G	0.9892	likely_pathogenic	0.9878	pathogenic	-2.579	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/H	0.9878	likely_pathogenic	0.983	pathogenic	-2.209	Highly Destabilizing	1.0	D	0.785	deleterious	D	0.658573841	None	None	N
Y/I	0.9269	likely_pathogenic	0.9123	pathogenic	-0.7	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
Y/K	0.9985	likely_pathogenic	0.9983	pathogenic	-1.952	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/L	0.8862	likely_pathogenic	0.8692	pathogenic	-0.7	Destabilizing	0.999	D	0.77	deleterious	None	None	None	None	N
Y/M	0.9731	likely_pathogenic	0.9657	pathogenic	-0.789	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
Y/N	0.9816	likely_pathogenic	0.9778	pathogenic	-2.913	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.658775646	None	None	N
Y/P	0.9991	likely_pathogenic	0.9991	pathogenic	-1.198	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
Y/Q	0.999	likely_pathogenic	0.9987	pathogenic	-2.414	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
Y/R	0.9963	likely_pathogenic	0.9955	pathogenic	-2.357	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
Y/S	0.9934	likely_pathogenic	0.9914	pathogenic	-3.109	Highly Destabilizing	1.0	D	0.893	deleterious	D	0.658775646	None	None	N
Y/T	0.995	likely_pathogenic	0.9934	pathogenic	-2.718	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
Y/V	0.9188	likely_pathogenic	0.9046	pathogenic	-1.198	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
Y/W	0.8874	likely_pathogenic	0.8678	pathogenic	-0.281	Destabilizing	1.0	D	0.778	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.