TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25815	77668;77669;77670	chr2:178568689;178568688;178568687	chr2:179433416;179433415;179433414
N2AB	24174	72745;72746;72747	chr2:178568689;178568688;178568687	chr2:179433416;179433415;179433414
N2A	23247	69964;69965;69966	chr2:178568689;178568688;178568687	chr2:179433416;179433415;179433414
N2B	16750	50473;50474;50475	chr2:178568689;178568688;178568687	chr2:179433416;179433415;179433414
Novex-1	16875	50848;50849;50850	chr2:178568689;178568688;178568687	chr2:179433416;179433415;179433414
Novex-2	16942	51049;51050;51051	chr2:178568689;178568688;178568687	chr2:179433416;179433415;179433414
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-136
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1701
• 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	rs777970390	-1.383	0.988	N	0.798	0.262	0.471700387322	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
L/F	rs777970390	-1.383	0.988	N	0.798	0.262	0.471700387322	gnomAD-4.0.0	2.05316E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69881E-06	0	0
L/W	None	None	0.999	N	0.821	0.495	0.720432007824	gnomAD-4.0.0	1.59222E-06	None	None	None	None	N	None	0	2.28781E-05	None	0	0	None	0	0	0	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	0.7366	likely_pathogenic	0.7666	pathogenic	-2.099	Highly Destabilizing	0.938	D	0.627	neutral	None	None	None	None	N
L/C	0.6797	likely_pathogenic	0.7101	pathogenic	-1.645	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
L/D	0.995	likely_pathogenic	0.9962	pathogenic	-1.26	Destabilizing	0.998	D	0.877	deleterious	None	None	None	None	N
L/E	0.9693	likely_pathogenic	0.9753	pathogenic	-1.123	Destabilizing	0.995	D	0.846	deleterious	None	None	None	None	N
L/F	0.3292	likely_benign	0.3746	ambiguous	-1.188	Destabilizing	0.988	D	0.798	deleterious	N	0.470165973	None	None	N
L/G	0.9522	likely_pathogenic	0.9617	pathogenic	-2.567	Highly Destabilizing	0.995	D	0.845	deleterious	None	None	None	None	N
L/H	0.8968	likely_pathogenic	0.9186	pathogenic	-1.67	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
L/I	0.1221	likely_benign	0.1213	benign	-0.814	Destabilizing	0.938	D	0.543	neutral	None	None	None	None	N
L/K	0.9277	likely_pathogenic	0.9391	pathogenic	-1.541	Destabilizing	0.995	D	0.836	deleterious	None	None	None	None	N
L/M	0.1518	likely_benign	0.1635	benign	-0.851	Destabilizing	0.994	D	0.769	deleterious	N	0.477509807	None	None	N
L/N	0.9706	likely_pathogenic	0.9779	pathogenic	-1.6	Destabilizing	0.998	D	0.875	deleterious	None	None	None	None	N
L/P	0.9937	likely_pathogenic	0.9948	pathogenic	-1.215	Destabilizing	0.998	D	0.87	deleterious	None	None	None	None	N
L/Q	0.8378	likely_pathogenic	0.8656	pathogenic	-1.558	Destabilizing	0.998	D	0.874	deleterious	None	None	None	None	N
L/R	0.8772	likely_pathogenic	0.8941	pathogenic	-1.146	Destabilizing	0.995	D	0.869	deleterious	None	None	None	None	N
L/S	0.9279	likely_pathogenic	0.9444	pathogenic	-2.422	Highly Destabilizing	0.994	D	0.842	deleterious	N	0.495867551	None	None	N
L/T	0.7436	likely_pathogenic	0.7805	pathogenic	-2.13	Highly Destabilizing	0.991	D	0.787	deleterious	None	None	None	None	N
L/V	0.1301	likely_benign	0.1304	benign	-1.215	Destabilizing	0.067	N	0.343	neutral	N	0.468884196	None	None	N
L/W	0.7851	likely_pathogenic	0.8293	pathogenic	-1.299	Destabilizing	0.999	D	0.821	deleterious	N	0.519251725	None	None	N
L/Y	0.8251	likely_pathogenic	0.8671	pathogenic	-1.08	Destabilizing	0.995	D	0.861	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.