TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21951	66076;66077;66078	chr2:178582952;178582951;178582950	chr2:179447679;179447678;179447677
N2AB	20310	61153;61154;61155	chr2:178582952;178582951;178582950	chr2:179447679;179447678;179447677
N2A	19383	58372;58373;58374	chr2:178582952;178582951;178582950	chr2:179447679;179447678;179447677
N2B	12886	38881;38882;38883	chr2:178582952;178582951;178582950	chr2:179447679;179447678;179447677
Novex-1	13011	39256;39257;39258	chr2:178582952;178582951;178582950	chr2:179447679;179447678;179447677
Novex-2	13078	39457;39458;39459	chr2:178582952;178582951;178582950	chr2:179447679;179447678;179447677
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-125
• Domain position: 86
• Structural Position: 174
• Q(SASA): 0.148
• 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
L/F	rs2048118733	None	0.998	N	0.757	0.489	0.746961985857	gnomAD-4.0.0	1.20037E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31256E-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
L/A	0.967	likely_pathogenic	0.9532	pathogenic	-2.63	Highly Destabilizing	0.992	D	0.699	prob.neutral	None	None	None	None	N
L/C	0.9063	likely_pathogenic	0.8798	pathogenic	-1.949	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
L/D	0.9996	likely_pathogenic	0.9994	pathogenic	-2.874	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/E	0.997	likely_pathogenic	0.9957	pathogenic	-2.569	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
L/F	0.7737	likely_pathogenic	0.6939	pathogenic	-1.616	Destabilizing	0.998	D	0.757	deleterious	N	0.512565542	None	None	N
L/G	0.993	likely_pathogenic	0.9892	pathogenic	-3.251	Highly Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
L/H	0.9944	likely_pathogenic	0.9901	pathogenic	-2.829	Highly Destabilizing	1.0	D	0.836	deleterious	D	0.525353879	None	None	N
L/I	0.1305	likely_benign	0.1258	benign	-0.796	Destabilizing	0.948	D	0.615	neutral	N	0.506462015	None	None	N
L/K	0.9939	likely_pathogenic	0.9906	pathogenic	-2.052	Highly Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
L/M	0.3396	likely_benign	0.3029	benign	-0.838	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
L/N	0.9967	likely_pathogenic	0.9951	pathogenic	-2.638	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
L/P	0.9972	likely_pathogenic	0.9949	pathogenic	-1.392	Destabilizing	0.999	D	0.856	deleterious	D	0.525353879	None	None	N
L/Q	0.99	likely_pathogenic	0.9843	pathogenic	-2.322	Highly Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
L/R	0.9898	likely_pathogenic	0.9837	pathogenic	-2.023	Highly Destabilizing	0.999	D	0.826	deleterious	D	0.525353879	None	None	N
L/S	0.9965	likely_pathogenic	0.9943	pathogenic	-3.356	Highly Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
L/T	0.964	likely_pathogenic	0.9483	pathogenic	-2.875	Highly Destabilizing	0.992	D	0.747	deleterious	None	None	None	None	N
L/V	0.1278	likely_benign	0.116	benign	-1.392	Destabilizing	0.333	N	0.296	neutral	N	0.436193853	None	None	N
L/W	0.9801	likely_pathogenic	0.9614	pathogenic	-1.998	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
L/Y	0.9783	likely_pathogenic	0.9613	pathogenic	-1.709	Destabilizing	1.0	D	0.787	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.