TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6644	20155;20156;20157	chr2:178727648;178727647;178727646	chr2:179592375;179592374;179592373
N2AB	6327	19204;19205;19206	chr2:178727648;178727647;178727646	chr2:179592375;179592374;179592373
N2A	5400	16423;16424;16425	chr2:178727648;178727647;178727646	chr2:179592375;179592374;179592373
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: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-50
• Domain position: 71
• Structural Position: 154
• Q(SASA): 0.0925
• 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/C	rs375417679	None	1.0	D	0.877	0.875	None	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	2.94E-05	None	0	0	None	0	None	0	0	0
Y/C	rs375417679	None	1.0	D	0.877	0.875	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
Y/C	rs375417679	None	1.0	D	0.877	0.875	None	gnomAD-4.0.0	1.86266E-06	None	None	None	None	N	None	0	5.04117E-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	0.9881	likely_pathogenic	0.9908	pathogenic	-1.919	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
Y/C	0.8905	likely_pathogenic	0.8894	pathogenic	-1.116	Destabilizing	1.0	D	0.877	deleterious	D	0.649012267	None	None	N
Y/D	0.9956	likely_pathogenic	0.9971	pathogenic	-2.667	Highly Destabilizing	1.0	D	0.877	deleterious	D	0.649012267	None	None	N
Y/E	0.9974	likely_pathogenic	0.9982	pathogenic	-2.416	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/F	0.1659	likely_benign	0.1669	benign	-0.609	Destabilizing	1.0	D	0.685	prob.neutral	D	0.585500952	None	None	N
Y/G	0.9837	likely_pathogenic	0.9875	pathogenic	-2.365	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
Y/H	0.9634	likely_pathogenic	0.9686	pathogenic	-2.05	Highly Destabilizing	1.0	D	0.787	deleterious	D	0.648810463	None	None	N
Y/I	0.7763	likely_pathogenic	0.7897	pathogenic	-0.443	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
Y/K	0.9977	likely_pathogenic	0.9983	pathogenic	-1.463	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
Y/L	0.7382	likely_pathogenic	0.775	pathogenic	-0.443	Destabilizing	0.999	D	0.78	deleterious	None	None	None	None	N
Y/M	0.9233	likely_pathogenic	0.9361	pathogenic	-0.565	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
Y/N	0.9715	likely_pathogenic	0.9784	pathogenic	-2.375	Highly Destabilizing	1.0	D	0.879	deleterious	D	0.649012267	None	None	N
Y/P	0.9978	likely_pathogenic	0.9985	pathogenic	-0.951	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
Y/Q	0.9967	likely_pathogenic	0.9974	pathogenic	-1.888	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
Y/R	0.9931	likely_pathogenic	0.9942	pathogenic	-1.923	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
Y/S	0.9846	likely_pathogenic	0.9883	pathogenic	-2.609	Highly Destabilizing	1.0	D	0.889	deleterious	D	0.649012267	None	None	N
Y/T	0.9905	likely_pathogenic	0.9927	pathogenic	-2.206	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/V	0.7039	likely_pathogenic	0.7269	pathogenic	-0.951	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
Y/W	0.858	likely_pathogenic	0.8723	pathogenic	-0.024	Destabilizing	1.0	D	0.781	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.