TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27019	81280;81281;81282	chr2:178565077;178565076;178565075	chr2:179429804;179429803;179429802
N2AB	25378	76357;76358;76359	chr2:178565077;178565076;178565075	chr2:179429804;179429803;179429802
N2A	24451	73576;73577;73578	chr2:178565077;178565076;178565075	chr2:179429804;179429803;179429802
N2B	17954	54085;54086;54087	chr2:178565077;178565076;178565075	chr2:179429804;179429803;179429802
Novex-1	18079	54460;54461;54462	chr2:178565077;178565076;178565075	chr2:179429804;179429803;179429802
Novex-2	18146	54661;54662;54663	chr2:178565077;178565076;178565075	chr2:179429804;179429803;179429802
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-84
• Domain position: 48
• Structural Position: 64
• Q(SASA): 0.5263
• 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
T/S	rs531674020	-0.523	0.027	N	0.276	0.085	0.107399877778	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
T/S	rs531674020	-0.523	0.027	N	0.276	0.085	0.107399877778	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	5.88E-05	0	0
T/S	rs531674020	-0.523	0.027	N	0.276	0.085	0.107399877778	gnomAD-4.0.0	1.59159E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8591E-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
T/A	0.0637	likely_benign	0.0637	benign	-0.609	Destabilizing	None	N	0.087	neutral	N	0.443213039	None	None	N
T/C	0.3631	ambiguous	0.342	ambiguous	-0.227	Destabilizing	0.935	D	0.224	neutral	None	None	None	None	N
T/D	0.3403	ambiguous	0.3678	ambiguous	-0.051	Destabilizing	0.081	N	0.223	neutral	None	None	None	None	N
T/E	0.3066	likely_benign	0.3345	benign	-0.094	Destabilizing	0.081	N	0.212	neutral	None	None	None	None	N
T/F	0.2262	likely_benign	0.2313	benign	-0.833	Destabilizing	0.38	N	0.287	neutral	None	None	None	None	N
T/G	0.1846	likely_benign	0.1837	benign	-0.809	Destabilizing	0.035	N	0.232	neutral	None	None	None	None	N
T/H	0.2572	likely_benign	0.254	benign	-1.032	Destabilizing	0.38	N	0.262	neutral	None	None	None	None	N
T/I	0.1163	likely_benign	0.1283	benign	-0.182	Destabilizing	0.062	N	0.28	neutral	N	0.497490241	None	None	N
T/K	0.2832	likely_benign	0.2996	benign	-0.643	Destabilizing	0.081	N	0.213	neutral	None	None	None	None	N
T/L	0.0801	likely_benign	0.0862	benign	-0.182	Destabilizing	0.001	N	0.225	neutral	None	None	None	None	N
T/M	0.0911	likely_benign	0.0881	benign	0.017	Stabilizing	0.38	N	0.223	neutral	None	None	None	None	N
T/N	0.0919	likely_benign	0.092	benign	-0.364	Destabilizing	None	N	0.098	neutral	N	0.436748427	None	None	N
T/P	0.4172	ambiguous	0.4319	ambiguous	-0.294	Destabilizing	0.484	N	0.255	neutral	N	0.511880903	None	None	N
T/Q	0.2381	likely_benign	0.2366	benign	-0.552	Destabilizing	0.38	N	0.261	neutral	None	None	None	None	N
T/R	0.2638	likely_benign	0.2806	benign	-0.333	Destabilizing	0.38	N	0.272	neutral	None	None	None	None	N
T/S	0.0842	likely_benign	0.084	benign	-0.589	Destabilizing	0.027	N	0.276	neutral	N	0.456024834	None	None	N
T/V	0.0862	likely_benign	0.0923	benign	-0.294	Destabilizing	0.035	N	0.207	neutral	None	None	None	None	N
T/W	0.6766	likely_pathogenic	0.6839	pathogenic	-0.822	Destabilizing	0.935	D	0.33	neutral	None	None	None	None	N
T/Y	0.2966	likely_benign	0.2957	benign	-0.597	Destabilizing	0.791	D	0.269	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.