TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28982	87169;87170;87171	chr2:178558515;178558514;178558513	chr2:179423242;179423241;179423240
N2AB	27341	82246;82247;82248	chr2:178558515;178558514;178558513	chr2:179423242;179423241;179423240
N2A	26414	79465;79466;79467	chr2:178558515;178558514;178558513	chr2:179423242;179423241;179423240
N2B	19917	59974;59975;59976	chr2:178558515;178558514;178558513	chr2:179423242;179423241;179423240
Novex-1	20042	60349;60350;60351	chr2:178558515;178558514;178558513	chr2:179423242;179423241;179423240
Novex-2	20109	60550;60551;60552	chr2:178558515;178558514;178558513	chr2:179423242;179423241;179423240
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-99
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.0866
• 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/P	rs767470225	None	0.781	N	0.797	0.308	0.716020962526	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

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	0.1861	likely_benign	0.189	benign	-2.195	Highly Destabilizing	0.25	N	0.52	neutral	None	None	None	None	N
L/C	0.3968	ambiguous	0.4032	ambiguous	-1.099	Destabilizing	0.947	D	0.7	prob.neutral	None	None	None	None	N
L/D	0.9155	likely_pathogenic	0.9277	pathogenic	-2.62	Highly Destabilizing	0.7	D	0.793	deleterious	None	None	None	None	N
L/E	0.4465	ambiguous	0.4461	ambiguous	-2.36	Highly Destabilizing	0.539	D	0.726	prob.delet.	None	None	None	None	N
L/F	0.1887	likely_benign	0.1995	benign	-1.246	Destabilizing	0.7	D	0.609	neutral	None	None	None	None	N
L/G	0.6178	likely_pathogenic	0.6357	pathogenic	-2.728	Highly Destabilizing	0.7	D	0.768	deleterious	None	None	None	None	N
L/H	0.3043	likely_benign	0.3284	benign	-2.402	Highly Destabilizing	0.947	D	0.758	deleterious	None	None	None	None	N
L/I	0.1072	likely_benign	0.105	benign	-0.63	Destabilizing	0.08	N	0.483	neutral	N	0.488446683	None	None	N
L/K	0.2121	likely_benign	0.2119	benign	-1.371	Destabilizing	0.539	D	0.677	prob.neutral	None	None	None	None	N
L/M	0.0731	likely_benign	0.0729	benign	-0.627	Destabilizing	0.7	D	0.621	neutral	None	None	None	None	N
L/N	0.6229	likely_pathogenic	0.6347	pathogenic	-1.818	Destabilizing	0.7	D	0.796	deleterious	None	None	None	None	N
L/P	0.9611	likely_pathogenic	0.9693	pathogenic	-1.137	Destabilizing	0.781	D	0.797	deleterious	N	0.47317921	None	None	N
L/Q	0.0893	likely_benign	0.09	benign	-1.592	Destabilizing	0.034	N	0.416	neutral	N	0.388223761	None	None	N
L/R	0.1389	likely_benign	0.1472	benign	-1.337	Destabilizing	0.468	N	0.738	prob.delet.	N	0.365173543	None	None	N
L/S	0.2916	likely_benign	0.2973	benign	-2.394	Highly Destabilizing	0.539	D	0.678	prob.neutral	None	None	None	None	N
L/T	0.2197	likely_benign	0.2132	benign	-2.0	Highly Destabilizing	0.539	D	0.679	prob.neutral	None	None	None	None	N
L/V	0.0831	likely_benign	0.08	benign	-1.137	Destabilizing	0.002	N	0.366	neutral	N	0.517806798	None	None	N
L/W	0.3127	likely_benign	0.3669	ambiguous	-1.715	Destabilizing	0.982	D	0.705	prob.neutral	None	None	None	None	N
L/Y	0.439	ambiguous	0.4755	ambiguous	-1.378	Destabilizing	0.826	D	0.741	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.