TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29292	88099;88100;88101	chr2:178557388;178557387;178557386	chr2:179422115;179422114;179422113
N2AB	27651	83176;83177;83178	chr2:178557388;178557387;178557386	chr2:179422115;179422114;179422113
N2A	26724	80395;80396;80397	chr2:178557388;178557387;178557386	chr2:179422115;179422114;179422113
N2B	20227	60904;60905;60906	chr2:178557388;178557387;178557386	chr2:179422115;179422114;179422113
Novex-1	20352	61279;61280;61281	chr2:178557388;178557387;178557386	chr2:179422115;179422114;179422113
Novex-2	20419	61480;61481;61482	chr2:178557388;178557387;178557386	chr2:179422115;179422114;179422113
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-101
• Domain position: 56
• Structural Position: 77
• Q(SASA): 0.0863
• 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
I/T	None	None	0.892	N	0.653	0.319	0.599966047421	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
I/V	rs1445509592	None	0.011	N	0.219	0.097	0.350307294319	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.92678E-04	None	0	0	0	0	0
I/V	rs1445509592	None	0.011	N	0.219	0.097	0.350307294319	gnomAD-4.0.0	2.56162E-06	None	None	None	None	N	None	0	0	None	0	4.84848E-05	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
I/A	0.8826	likely_pathogenic	0.8888	pathogenic	-2.344	Highly Destabilizing	0.845	D	0.529	neutral	None	None	None	None	N
I/C	0.8529	likely_pathogenic	0.8781	pathogenic	-1.368	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
I/D	0.9952	likely_pathogenic	0.9949	pathogenic	-2.812	Highly Destabilizing	0.996	D	0.785	deleterious	None	None	None	None	N
I/E	0.9858	likely_pathogenic	0.9833	pathogenic	-2.561	Highly Destabilizing	0.987	D	0.781	deleterious	None	None	None	None	N
I/F	0.6666	likely_pathogenic	0.6876	pathogenic	-1.389	Destabilizing	0.967	D	0.677	prob.neutral	N	0.488939607	None	None	N
I/G	0.9781	likely_pathogenic	0.9789	pathogenic	-2.897	Highly Destabilizing	0.987	D	0.78	deleterious	None	None	None	None	N
I/H	0.9752	likely_pathogenic	0.977	pathogenic	-2.517	Highly Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
I/K	0.9732	likely_pathogenic	0.9724	pathogenic	-1.724	Destabilizing	0.987	D	0.781	deleterious	None	None	None	None	N
I/L	0.2173	likely_benign	0.2417	benign	-0.731	Destabilizing	0.426	N	0.359	neutral	N	0.469100606	None	None	N
I/M	0.272	likely_benign	0.2755	benign	-0.598	Destabilizing	0.983	D	0.674	neutral	N	0.498663298	None	None	N
I/N	0.9037	likely_pathogenic	0.8932	pathogenic	-2.136	Highly Destabilizing	0.994	D	0.801	deleterious	N	0.50242228	None	None	N
I/P	0.9622	likely_pathogenic	0.9708	pathogenic	-1.252	Destabilizing	0.996	D	0.795	deleterious	None	None	None	None	N
I/Q	0.9575	likely_pathogenic	0.9568	pathogenic	-1.945	Destabilizing	0.996	D	0.803	deleterious	None	None	None	None	N
I/R	0.9602	likely_pathogenic	0.9594	pathogenic	-1.572	Destabilizing	0.987	D	0.8	deleterious	None	None	None	None	N
I/S	0.8815	likely_pathogenic	0.8803	pathogenic	-2.763	Highly Destabilizing	0.983	D	0.7	prob.neutral	N	0.466272541	None	None	N
I/T	0.8644	likely_pathogenic	0.8496	pathogenic	-2.368	Highly Destabilizing	0.892	D	0.653	neutral	N	0.463794233	None	None	N
I/V	0.1801	likely_benign	0.1875	benign	-1.252	Destabilizing	0.011	N	0.219	neutral	N	0.450792372	None	None	N
I/W	0.9855	likely_pathogenic	0.9881	pathogenic	-1.878	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
I/Y	0.9585	likely_pathogenic	0.9599	pathogenic	-1.532	Destabilizing	0.987	D	0.715	prob.delet.	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.