TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30063	90412;90413;90414	chr2:178552713;178552712;178552711	chr2:179417440;179417439;179417438
N2AB	28422	85489;85490;85491	chr2:178552713;178552712;178552711	chr2:179417440;179417439;179417438
N2A	27495	82708;82709;82710	chr2:178552713;178552712;178552711	chr2:179417440;179417439;179417438
N2B	20998	63217;63218;63219	chr2:178552713;178552712;178552711	chr2:179417440;179417439;179417438
Novex-1	21123	63592;63593;63594	chr2:178552713;178552712;178552711	chr2:179417440;179417439;179417438
Novex-2	21190	63793;63794;63795	chr2:178552713;178552712;178552711	chr2:179417440;179417439;179417438
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: Fn3-107
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.3414
• Predicted PPI site: I

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	rs770325813	0.062	0.984	N	0.467	0.369	0.441221003447	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
T/I	rs770325813	0.062	0.984	N	0.467	0.369	0.441221003447	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
T/I	rs770325813	0.062	0.984	N	0.467	0.369	0.441221003447	gnomAD-4.0.0	2.47875E-06	None	None	None	None	I	None	2.67001E-05	0	None	0	0	None	0	0	1.69522E-06	0	0
T/K	None	None	0.896	N	0.393	0.376	0.419957187557	gnomAD-4.0.0	6.84199E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15931E-05	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	0.0951	likely_benign	0.0915	benign	-0.477	Destabilizing	0.64	D	0.431	neutral	N	0.49622467	None	None	I
T/C	0.3815	ambiguous	0.3631	ambiguous	-0.333	Destabilizing	0.999	D	0.486	neutral	None	None	None	None	I
T/D	0.4397	ambiguous	0.4109	ambiguous	0.131	Stabilizing	0.851	D	0.406	neutral	None	None	None	None	I
T/E	0.3224	likely_benign	0.314	benign	0.095	Stabilizing	0.919	D	0.397	neutral	None	None	None	None	I
T/F	0.2732	likely_benign	0.252	benign	-0.651	Destabilizing	0.996	D	0.556	neutral	None	None	None	None	I
T/G	0.2197	likely_benign	0.2021	benign	-0.685	Destabilizing	0.702	D	0.478	neutral	None	None	None	None	I
T/H	0.293	likely_benign	0.2737	benign	-0.894	Destabilizing	0.988	D	0.54	neutral	None	None	None	None	I
T/I	0.1606	likely_benign	0.1599	benign	-0.032	Destabilizing	0.984	D	0.467	neutral	N	0.475829464	None	None	I
T/K	0.2093	likely_benign	0.2042	benign	-0.568	Destabilizing	0.896	D	0.393	neutral	N	0.480246782	None	None	I
T/L	0.0867	likely_benign	0.0853	benign	-0.032	Destabilizing	0.919	D	0.399	neutral	None	None	None	None	I
T/M	0.089	likely_benign	0.0887	benign	0.056	Stabilizing	0.999	D	0.485	neutral	None	None	None	None	I
T/N	0.132	likely_benign	0.124	benign	-0.358	Destabilizing	0.132	N	0.151	neutral	None	None	None	None	I
T/P	0.2991	likely_benign	0.259	benign	-0.149	Destabilizing	0.984	D	0.455	neutral	D	0.534207607	None	None	I
T/Q	0.242	likely_benign	0.2342	benign	-0.532	Destabilizing	0.988	D	0.504	neutral	None	None	None	None	I
T/R	0.1855	likely_benign	0.1744	benign	-0.295	Destabilizing	0.968	D	0.453	neutral	N	0.489236458	None	None	I
T/S	0.1044	likely_benign	0.0998	benign	-0.616	Destabilizing	0.046	N	0.077	neutral	N	0.47842313	None	None	I
T/V	0.138	likely_benign	0.1358	benign	-0.149	Destabilizing	0.919	D	0.397	neutral	None	None	None	None	I
T/W	0.5857	likely_pathogenic	0.5465	ambiguous	-0.627	Destabilizing	0.999	D	0.671	neutral	None	None	None	None	I
T/Y	0.3222	likely_benign	0.297	benign	-0.387	Destabilizing	0.996	D	0.557	neutral	None	None	None	None	I

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.