TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20307	61144;61145;61146	chr2:178590806;178590805;178590804	chr2:179455533;179455532;179455531
N2AB	18666	56221;56222;56223	chr2:178590806;178590805;178590804	chr2:179455533;179455532;179455531
N2A	17739	53440;53441;53442	chr2:178590806;178590805;178590804	chr2:179455533;179455532;179455531
N2B	11242	33949;33950;33951	chr2:178590806;178590805;178590804	chr2:179455533;179455532;179455531
Novex-1	11367	34324;34325;34326	chr2:178590806;178590805;178590804	chr2:179455533;179455532;179455531
Novex-2	11434	34525;34526;34527	chr2:178590806;178590805;178590804	chr2:179455533;179455532;179455531
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-35
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.1761
• 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
Y/C	None	None	0.975	N	0.553	0.369	0.615085622779	gnomAD-4.0.0	6.87165E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.03551E-07	0	0
Y/F	rs1553643111	None	0.425	N	0.445	0.171	0.351180957027	gnomAD-4.0.0	1.37433E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.8071E-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
Y/A	0.5489	ambiguous	0.5355	ambiguous	-3.095	Highly Destabilizing	0.495	N	0.549	neutral	None	None	None	None	N
Y/C	0.0932	likely_benign	0.0982	benign	-1.523	Destabilizing	0.975	D	0.553	neutral	N	0.476768252	None	None	N
Y/D	0.6296	likely_pathogenic	0.6695	pathogenic	-2.834	Highly Destabilizing	0.975	D	0.599	neutral	N	0.456526266	None	None	N
Y/E	0.7651	likely_pathogenic	0.7737	pathogenic	-2.661	Highly Destabilizing	0.936	D	0.551	neutral	None	None	None	None	N
Y/F	0.0698	likely_benign	0.0635	benign	-1.154	Destabilizing	0.425	N	0.445	neutral	N	0.437287144	None	None	N
Y/G	0.6785	likely_pathogenic	0.6826	pathogenic	-3.471	Highly Destabilizing	0.936	D	0.559	neutral	None	None	None	None	N
Y/H	0.1093	likely_benign	0.114	benign	-1.867	Destabilizing	0.975	D	0.558	neutral	N	0.41214077	None	None	N
Y/I	0.1749	likely_benign	0.1548	benign	-1.862	Destabilizing	0.001	N	0.35	neutral	None	None	None	None	N
Y/K	0.692	likely_pathogenic	0.6733	pathogenic	-1.97	Destabilizing	0.828	D	0.551	neutral	None	None	None	None	N
Y/L	0.2802	likely_benign	0.2537	benign	-1.862	Destabilizing	0.001	N	0.349	neutral	None	None	None	None	N
Y/M	0.434	ambiguous	0.3758	ambiguous	-1.498	Destabilizing	0.893	D	0.593	neutral	None	None	None	None	N
Y/N	0.2586	likely_benign	0.2558	benign	-2.559	Highly Destabilizing	0.975	D	0.585	neutral	N	0.446213272	None	None	N
Y/P	0.9728	likely_pathogenic	0.9753	pathogenic	-2.284	Highly Destabilizing	0.981	D	0.606	neutral	None	None	None	None	N
Y/Q	0.487	ambiguous	0.4918	ambiguous	-2.406	Highly Destabilizing	0.981	D	0.593	neutral	None	None	None	None	N
Y/R	0.4816	ambiguous	0.4848	ambiguous	-1.565	Destabilizing	0.944	D	0.583	neutral	None	None	None	None	N
Y/S	0.2666	likely_benign	0.2625	benign	-2.977	Highly Destabilizing	0.784	D	0.559	neutral	N	0.446423916	None	None	N
Y/T	0.3863	ambiguous	0.3669	ambiguous	-2.703	Highly Destabilizing	0.495	N	0.551	neutral	None	None	None	None	N
Y/V	0.1754	likely_benign	0.1584	benign	-2.284	Highly Destabilizing	0.085	N	0.463	neutral	None	None	None	None	N
Y/W	0.269	likely_benign	0.2732	benign	-0.457	Destabilizing	0.981	D	0.58	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.