TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18107	54544;54545;54546	chr2:178604770;178604769;178604768	chr2:179469497;179469496;179469495
N2AB	16466	49621;49622;49623	chr2:178604770;178604769;178604768	chr2:179469497;179469496;179469495
N2A	15539	46840;46841;46842	chr2:178604770;178604769;178604768	chr2:179469497;179469496;179469495
N2B	9042	27349;27350;27351	chr2:178604770;178604769;178604768	chr2:179469497;179469496;179469495
Novex-1	9167	27724;27725;27726	chr2:178604770;178604769;178604768	chr2:179469497;179469496;179469495
Novex-2	9234	27925;27926;27927	chr2:178604770;178604769;178604768	chr2:179469497;179469496;179469495
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-19
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.2422
• 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
A/G	rs794729457	None	0.98	N	0.548	0.243	0.236890367714	gnomAD-4.0.0	3.18959E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72971E-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
A/C	0.4735	ambiguous	0.4446	ambiguous	-1.152	Destabilizing	1.0	D	0.585	neutral	None	None	None	None	N
A/D	0.6619	likely_pathogenic	0.6206	pathogenic	-1.552	Destabilizing	0.942	D	0.573	neutral	None	None	None	None	N
A/E	0.6194	likely_pathogenic	0.5774	pathogenic	-1.617	Destabilizing	0.248	N	0.376	neutral	N	0.448696217	None	None	N
A/F	0.4337	ambiguous	0.4028	ambiguous	-1.278	Destabilizing	0.996	D	0.637	neutral	None	None	None	None	N
A/G	0.1748	likely_benign	0.1648	benign	-1.296	Destabilizing	0.98	D	0.548	neutral	N	0.469015561	None	None	N
A/H	0.7321	likely_pathogenic	0.7128	pathogenic	-1.174	Destabilizing	1.0	D	0.642	neutral	None	None	None	None	N
A/I	0.2221	likely_benign	0.2157	benign	-0.698	Destabilizing	0.942	D	0.531	neutral	None	None	None	None	N
A/K	0.7946	likely_pathogenic	0.7603	pathogenic	-1.205	Destabilizing	0.97	D	0.54	neutral	None	None	None	None	N
A/L	0.2433	likely_benign	0.2327	benign	-0.698	Destabilizing	0.871	D	0.523	neutral	None	None	None	None	N
A/M	0.3107	likely_benign	0.2907	benign	-0.574	Destabilizing	0.996	D	0.585	neutral	None	None	None	None	N
A/N	0.4635	ambiguous	0.4327	ambiguous	-0.952	Destabilizing	0.996	D	0.63	neutral	None	None	None	None	N
A/P	0.4948	ambiguous	0.4777	ambiguous	-0.793	Destabilizing	0.998	D	0.575	neutral	N	0.489852193	None	None	N
A/Q	0.6478	likely_pathogenic	0.6292	pathogenic	-1.239	Destabilizing	0.991	D	0.574	neutral	None	None	None	None	N
A/R	0.745	likely_pathogenic	0.7082	pathogenic	-0.718	Destabilizing	0.991	D	0.575	neutral	None	None	None	None	N
A/S	0.115	likely_benign	0.1138	benign	-1.279	Destabilizing	0.961	D	0.557	neutral	N	0.471573076	None	None	N
A/T	0.1175	likely_benign	0.1104	benign	-1.268	Destabilizing	0.961	D	0.548	neutral	N	0.459913288	None	None	N
A/V	0.1199	likely_benign	0.1172	benign	-0.793	Destabilizing	0.122	N	0.236	neutral	N	0.454179394	None	None	N
A/W	0.8451	likely_pathogenic	0.8262	pathogenic	-1.464	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
A/Y	0.6119	likely_pathogenic	0.599	pathogenic	-1.129	Destabilizing	0.999	D	0.639	neutral	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.