TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32063	96412;96413;96414	chr2:178543957;178543956;178543955	chr2:179408684;179408683;179408682
N2AB	30422	91489;91490;91491	chr2:178543957;178543956;178543955	chr2:179408684;179408683;179408682
N2A	29495	88708;88709;88710	chr2:178543957;178543956;178543955	chr2:179408684;179408683;179408682
N2B	22998	69217;69218;69219	chr2:178543957;178543956;178543955	chr2:179408684;179408683;179408682
Novex-1	23123	69592;69593;69594	chr2:178543957;178543956;178543955	chr2:179408684;179408683;179408682
Novex-2	23190	69793;69794;69795	chr2:178543957;178543956;178543955	chr2:179408684;179408683;179408682
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-153
• Domain position: 47
• Structural Position: 127
• Q(SASA): 0.4592
• 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/A	None	None	0.22	D	0.566	0.198	0.280181792013	gnomAD-4.0.0	1.59141E-06	None	None	None	None	N	None	0	0	None	0	2.77269E-05	None	0	0	0	0	0
T/N	None	None	0.001	N	0.31	0.149	0.148003135375	gnomAD-4.0.0	1.36847E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79902E-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	0.083	likely_benign	0.0829	benign	-0.878	Destabilizing	0.22	N	0.566	neutral	D	0.527226863	None	None	N
T/C	0.2771	likely_benign	0.2872	benign	-0.389	Destabilizing	0.968	D	0.672	neutral	None	None	None	None	N
T/D	0.3458	ambiguous	0.3499	ambiguous	0.358	Stabilizing	0.157	N	0.621	neutral	None	None	None	None	N
T/E	0.3407	ambiguous	0.3368	benign	0.345	Stabilizing	0.396	N	0.625	neutral	None	None	None	None	N
T/F	0.2697	likely_benign	0.2539	benign	-1.058	Destabilizing	0.567	D	0.744	deleterious	None	None	None	None	N
T/G	0.2361	likely_benign	0.2378	benign	-1.106	Destabilizing	0.157	N	0.703	prob.neutral	None	None	None	None	N
T/H	0.1956	likely_benign	0.2051	benign	-1.314	Destabilizing	0.832	D	0.745	deleterious	None	None	None	None	N
T/I	0.1515	likely_benign	0.1464	benign	-0.368	Destabilizing	0.002	N	0.393	neutral	N	0.512990916	None	None	N
T/K	0.2256	likely_benign	0.2222	benign	-0.469	Destabilizing	0.396	N	0.636	neutral	None	None	None	None	N
T/L	0.1224	likely_benign	0.1155	benign	-0.368	Destabilizing	0.157	N	0.602	neutral	None	None	None	None	N
T/M	0.1006	likely_benign	0.1012	benign	-0.089	Destabilizing	0.832	D	0.658	neutral	None	None	None	None	N
T/N	0.0764	likely_benign	0.0753	benign	-0.334	Destabilizing	0.001	N	0.31	neutral	N	0.460772584	None	None	N
T/P	0.3177	likely_benign	0.2858	benign	-0.507	Destabilizing	0.667	D	0.673	neutral	D	0.530845958	None	None	N
T/Q	0.2277	likely_benign	0.2359	benign	-0.49	Destabilizing	0.567	D	0.667	neutral	None	None	None	None	N
T/R	0.1912	likely_benign	0.1852	benign	-0.27	Destabilizing	0.567	D	0.678	prob.neutral	None	None	None	None	N
T/S	0.0885	likely_benign	0.0891	benign	-0.706	Destabilizing	0.124	N	0.569	neutral	N	0.467853272	None	None	N
T/V	0.1168	likely_benign	0.1169	benign	-0.507	Destabilizing	0.157	N	0.562	neutral	None	None	None	None	N
T/W	0.6669	likely_pathogenic	0.6531	pathogenic	-0.955	Destabilizing	0.968	D	0.749	deleterious	None	None	None	None	N
T/Y	0.253	likely_benign	0.2481	benign	-0.725	Destabilizing	0.89	D	0.749	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.