TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27530	82813;82814;82815	chr2:178563544;178563543;178563542	chr2:179428271;179428270;179428269
N2AB	25889	77890;77891;77892	chr2:178563544;178563543;178563542	chr2:179428271;179428270;179428269
N2A	24962	75109;75110;75111	chr2:178563544;178563543;178563542	chr2:179428271;179428270;179428269
N2B	18465	55618;55619;55620	chr2:178563544;178563543;178563542	chr2:179428271;179428270;179428269
Novex-1	18590	55993;55994;55995	chr2:178563544;178563543;178563542	chr2:179428271;179428270;179428269
Novex-2	18657	56194;56195;56196	chr2:178563544;178563543;178563542	chr2:179428271;179428270;179428269
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Fn3-88
• Domain position: 62
• Structural Position: 92
• Q(SASA): 0.6045
• 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
R/K	None	None	0.997	N	0.544	0.324	0.344483371355	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
R/T	None	None	1.0	N	0.745	0.343	0.399017061211	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
R/A	0.8576	likely_pathogenic	0.8091	pathogenic	-0.401	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
R/C	0.4559	ambiguous	0.3803	ambiguous	-0.48	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
R/D	0.9659	likely_pathogenic	0.9498	pathogenic	-0.011	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
R/E	0.8431	likely_pathogenic	0.7979	pathogenic	0.065	Stabilizing	0.999	D	0.66	neutral	None	None	None	None	N
R/F	0.9012	likely_pathogenic	0.8668	pathogenic	-0.573	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
R/G	0.815	likely_pathogenic	0.7551	pathogenic	-0.626	Destabilizing	1.0	D	0.693	prob.neutral	N	0.492853628	None	None	N
R/H	0.2557	likely_benign	0.2115	benign	-1.0	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
R/I	0.7308	likely_pathogenic	0.6691	pathogenic	0.167	Stabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
R/K	0.1841	likely_benign	0.1536	benign	-0.408	Destabilizing	0.997	D	0.544	neutral	N	0.420874897	None	None	N
R/L	0.5983	likely_pathogenic	0.5278	ambiguous	0.167	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
R/M	0.7059	likely_pathogenic	0.6312	pathogenic	-0.137	Destabilizing	1.0	D	0.775	deleterious	N	0.473735415	None	None	N
R/N	0.9356	likely_pathogenic	0.9081	pathogenic	-0.035	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
R/P	0.8662	likely_pathogenic	0.802	pathogenic	-0.001	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
R/Q	0.2929	likely_benign	0.2433	benign	-0.22	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
R/S	0.912	likely_pathogenic	0.8848	pathogenic	-0.623	Destabilizing	1.0	D	0.753	deleterious	N	0.509571317	None	None	N
R/T	0.7194	likely_pathogenic	0.6593	pathogenic	-0.396	Destabilizing	1.0	D	0.745	deleterious	N	0.444476902	None	None	N
R/V	0.7579	likely_pathogenic	0.7044	pathogenic	-0.001	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
R/W	0.4375	ambiguous	0.3837	ambiguous	-0.454	Destabilizing	1.0	D	0.805	deleterious	N	0.511046788	None	None	N
R/Y	0.7781	likely_pathogenic	0.7175	pathogenic	-0.078	Destabilizing	1.0	D	0.779	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.