TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6305	19138;19139;19140	chr2:178729125;178729124;178729123	chr2:179593852;179593851;179593850
N2AB	5988	18187;18188;18189	chr2:178729125;178729124;178729123	chr2:179593852;179593851;179593850
N2A	5061	15406;15407;15408	chr2:178729125;178729124;178729123	chr2:179593852;179593851;179593850
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-47
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.4845
• 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	rs1197830521	None	0.391	N	0.289	0.109	0.359963025489	gnomAD-4.0.0	6.87102E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.66362E-05
L/W	rs1267771409	-1.331	1.0	N	0.637	0.403	0.758618040938	gnomAD-2.1.1	4.18E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.27E-06	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	0.2051	likely_benign	0.1807	benign	-1.238	Destabilizing	0.992	D	0.444	neutral	None	None	None	None	N
L/C	0.5188	ambiguous	0.4851	ambiguous	-0.691	Destabilizing	1.0	D	0.489	neutral	None	None	None	None	N
L/D	0.6445	likely_pathogenic	0.6142	pathogenic	-0.596	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
L/E	0.2826	likely_benign	0.2652	benign	-0.656	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
L/F	0.1423	likely_benign	0.1285	benign	-1.007	Destabilizing	0.391	N	0.289	neutral	N	0.460642865	None	None	N
L/G	0.4457	ambiguous	0.4075	ambiguous	-1.486	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
L/H	0.2482	likely_benign	0.2376	benign	-0.693	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
L/I	0.1101	likely_benign	0.0986	benign	-0.673	Destabilizing	0.983	D	0.387	neutral	None	None	None	None	N
L/K	0.2049	likely_benign	0.1991	benign	-0.732	Destabilizing	1.0	D	0.585	neutral	None	None	None	None	N
L/M	0.1288	likely_benign	0.1185	benign	-0.469	Destabilizing	0.998	D	0.439	neutral	N	0.460896354	None	None	N
L/N	0.3833	ambiguous	0.338	benign	-0.446	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	N
L/P	0.2651	likely_benign	0.2506	benign	-0.828	Destabilizing	1.0	D	0.66	neutral	None	None	None	None	N
L/Q	0.1231	likely_benign	0.1162	benign	-0.695	Destabilizing	1.0	D	0.58	neutral	None	None	None	None	N
L/R	0.154	likely_benign	0.1576	benign	-0.1	Destabilizing	1.0	D	0.587	neutral	None	None	None	None	N
L/S	0.2135	likely_benign	0.1872	benign	-0.998	Destabilizing	0.998	D	0.585	neutral	N	0.479989411	None	None	N
L/T	0.2228	likely_benign	0.1983	benign	-0.947	Destabilizing	0.998	D	0.461	neutral	None	None	None	None	N
L/V	0.1093	likely_benign	0.0995	benign	-0.828	Destabilizing	0.543	D	0.315	neutral	N	0.380497207	None	None	N
L/W	0.2101	likely_benign	0.2029	benign	-1.009	Destabilizing	1.0	D	0.637	neutral	N	0.476291584	None	None	N
L/Y	0.3357	likely_benign	0.3131	benign	-0.79	Destabilizing	0.995	D	0.484	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.