TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10009	30250;30251;30252	chr2:178704345;178704344;178704343	chr2:179569072;179569071;179569070
N2AB	9692	29299;29300;29301	chr2:178704345;178704344;178704343	chr2:179569072;179569071;179569070
N2A	8765	26518;26519;26520	chr2:178704345;178704344;178704343	chr2:179569072;179569071;179569070
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-85
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.2171
• 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/I	None	None	0.193	None	0.597	0.243	0.626364337782	gnomAD-4.0.0	1.59086E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85747E-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	0.1222	likely_benign	0.1434	benign	-0.994	Destabilizing	0.001	N	0.329	neutral	None	None	None	None	N
T/C	0.7317	likely_pathogenic	0.7871	pathogenic	-0.624	Destabilizing	0.944	D	0.615	neutral	None	None	None	None	N
T/D	0.5487	ambiguous	0.5665	pathogenic	-0.848	Destabilizing	0.388	N	0.59	neutral	None	None	None	None	N
T/E	0.3725	ambiguous	0.3888	ambiguous	-0.764	Destabilizing	0.388	N	0.583	neutral	None	None	None	None	N
T/F	0.3255	likely_benign	0.3802	ambiguous	-0.709	Destabilizing	0.69	D	0.623	neutral	None	None	None	None	N
T/G	0.5035	ambiguous	0.5692	pathogenic	-1.347	Destabilizing	0.241	N	0.625	neutral	None	None	None	None	N
T/H	0.3521	ambiguous	0.4189	ambiguous	-1.556	Destabilizing	0.981	D	0.649	neutral	None	None	None	None	N
T/I	0.162	likely_benign	0.2054	benign	-0.111	Destabilizing	0.193	N	0.597	neutral	None	None	None	None	N
T/K	0.3127	likely_benign	0.3553	ambiguous	-0.933	Destabilizing	0.324	N	0.591	neutral	None	None	None	None	N
T/L	0.1496	likely_benign	0.1809	benign	-0.111	Destabilizing	0.116	N	0.587	neutral	None	None	None	None	N
T/M	0.1116	likely_benign	0.1273	benign	0.107	Stabilizing	0.818	D	0.627	neutral	None	None	None	None	N
T/N	0.1781	likely_benign	0.1982	benign	-1.121	Destabilizing	0.388	N	0.601	neutral	None	None	None	None	N
T/P	0.4974	ambiguous	0.6242	pathogenic	-0.372	Destabilizing	0.627	D	0.623	neutral	None	None	None	None	N
T/Q	0.3084	likely_benign	0.3432	ambiguous	-1.123	Destabilizing	0.818	D	0.621	neutral	None	None	None	None	N
T/R	0.2592	likely_benign	0.2991	benign	-0.835	Destabilizing	0.627	D	0.619	neutral	None	None	None	None	N
T/S	0.1603	likely_benign	0.1774	benign	-1.365	Destabilizing	0.003	N	0.339	neutral	None	None	None	None	N
T/V	0.1695	likely_benign	0.1992	benign	-0.372	Destabilizing	0.002	N	0.365	neutral	None	None	None	None	N
T/W	0.7602	likely_pathogenic	0.8058	pathogenic	-0.728	Destabilizing	0.981	D	0.69	prob.neutral	None	None	None	None	N
T/Y	0.3957	ambiguous	0.4506	ambiguous	-0.478	Destabilizing	0.818	D	0.649	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.