TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26857	80794;80795;80796	chr2:178565563;178565562;178565561	chr2:179430290;179430289;179430288
N2AB	25216	75871;75872;75873	chr2:178565563;178565562;178565561	chr2:179430290;179430289;179430288
N2A	24289	73090;73091;73092	chr2:178565563;178565562;178565561	chr2:179430290;179430289;179430288
N2B	17792	53599;53600;53601	chr2:178565563;178565562;178565561	chr2:179430290;179430289;179430288
Novex-1	17917	53974;53975;53976	chr2:178565563;178565562;178565561	chr2:179430290;179430289;179430288
Novex-2	17984	54175;54176;54177	chr2:178565563;178565562;178565561	chr2:179430290;179430289;179430288
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-83
• Domain position: 78
• Structural Position: 112
• Q(SASA): 0.072
• 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
N/D	None	None	0.999	N	0.611	0.692	0.423480098753	gnomAD-4.0.0	1.59166E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43287E-05	0
N/K	None	None	1.0	D	0.77	0.551	0.210429274316	gnomAD-4.0.0	6.84302E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99598E-07	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
N/A	0.9891	likely_pathogenic	0.9905	pathogenic	-1.22	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
N/C	0.9182	likely_pathogenic	0.9176	pathogenic	-0.846	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
N/D	0.9813	likely_pathogenic	0.9807	pathogenic	-2.271	Highly Destabilizing	0.999	D	0.611	neutral	N	0.521396498	None	None	N
N/E	0.9974	likely_pathogenic	0.9972	pathogenic	-2.043	Highly Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
N/F	0.9985	likely_pathogenic	0.9987	pathogenic	-0.819	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
N/G	0.9638	likely_pathogenic	0.9705	pathogenic	-1.575	Destabilizing	1.0	D	0.577	neutral	None	None	None	None	N
N/H	0.9399	likely_pathogenic	0.9466	pathogenic	-1.104	Destabilizing	1.0	D	0.775	deleterious	D	0.545287651	None	None	N
N/I	0.9892	likely_pathogenic	0.9896	pathogenic	-0.28	Destabilizing	1.0	D	0.837	deleterious	D	0.53904668	None	None	N
N/K	0.997	likely_pathogenic	0.9968	pathogenic	-0.514	Destabilizing	1.0	D	0.77	deleterious	D	0.526422927	None	None	N
N/L	0.9526	likely_pathogenic	0.964	pathogenic	-0.28	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
N/M	0.9907	likely_pathogenic	0.9924	pathogenic	-0.147	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
N/P	0.9916	likely_pathogenic	0.992	pathogenic	-0.568	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
N/Q	0.9955	likely_pathogenic	0.9956	pathogenic	-1.217	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
N/R	0.9909	likely_pathogenic	0.9899	pathogenic	-0.624	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
N/S	0.5993	likely_pathogenic	0.6293	pathogenic	-1.47	Destabilizing	1.0	D	0.593	neutral	N	0.503061525	None	None	N
N/T	0.904	likely_pathogenic	0.9288	pathogenic	-1.079	Destabilizing	1.0	D	0.736	prob.delet.	N	0.503449465	None	None	N
N/V	0.9848	likely_pathogenic	0.9859	pathogenic	-0.568	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
N/W	0.9993	likely_pathogenic	0.9993	pathogenic	-0.803	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
N/Y	0.9872	likely_pathogenic	0.988	pathogenic	-0.435	Destabilizing	1.0	D	0.861	deleterious	D	0.556897445	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.