TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26452	79579;79580;79581	chr2:178566778;178566777;178566776	chr2:179431505;179431504;179431503
N2AB	24811	74656;74657;74658	chr2:178566778;178566777;178566776	chr2:179431505;179431504;179431503
N2A	23884	71875;71876;71877	chr2:178566778;178566777;178566776	chr2:179431505;179431504;179431503
N2B	17387	52384;52385;52386	chr2:178566778;178566777;178566776	chr2:179431505;179431504;179431503
Novex-1	17512	52759;52760;52761	chr2:178566778;178566777;178566776	chr2:179431505;179431504;179431503
Novex-2	17579	52960;52961;52962	chr2:178566778;178566777;178566776	chr2:179431505;179431504;179431503
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: Fn3-80
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.343
• 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/K	rs375061238	None	0.999	N	0.592	0.503	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/K	rs375061238	None	0.999	N	0.592	0.503	None	gnomAD-4.0.0	6.57618E-06	None	None	None	None	N	None	2.41359E-05	0	None	0	0	None	0	0	0	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	0.0998	likely_benign	0.0763	benign	-0.912	Destabilizing	0.996	D	0.353	neutral	N	0.495162012	None	None	N
T/C	0.4433	ambiguous	0.3692	ambiguous	-0.423	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	N
T/D	0.7618	likely_pathogenic	0.7108	pathogenic	-0.353	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
T/E	0.6046	likely_pathogenic	0.5721	pathogenic	-0.332	Destabilizing	1.0	D	0.603	neutral	None	None	None	None	N
T/F	0.3853	ambiguous	0.3294	benign	-0.885	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
T/G	0.3281	likely_benign	0.2453	benign	-1.198	Destabilizing	1.0	D	0.583	neutral	None	None	None	None	N
T/H	0.4208	ambiguous	0.3815	ambiguous	-1.387	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	N
T/I	0.1695	likely_benign	0.1539	benign	-0.23	Destabilizing	0.998	D	0.587	neutral	N	0.454643541	None	None	N
T/K	0.4455	ambiguous	0.4517	ambiguous	-0.841	Destabilizing	0.999	D	0.592	neutral	N	0.454198037	None	None	N
T/L	0.0831	likely_benign	0.082	benign	-0.23	Destabilizing	0.994	D	0.399	neutral	None	None	None	None	N
T/M	0.0795	likely_benign	0.0737	benign	0.04	Stabilizing	0.985	D	0.343	neutral	None	None	None	None	N
T/N	0.1959	likely_benign	0.1554	benign	-0.794	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	N
T/P	0.3525	ambiguous	0.2437	benign	-0.425	Destabilizing	1.0	D	0.657	neutral	D	0.522868688	None	None	N
T/Q	0.3269	likely_benign	0.3064	benign	-0.881	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
T/R	0.3911	ambiguous	0.3837	ambiguous	-0.606	Destabilizing	0.999	D	0.658	neutral	N	0.463798955	None	None	N
T/S	0.1496	likely_benign	0.1204	benign	-1.056	Destabilizing	0.998	D	0.355	neutral	N	0.464455103	None	None	N
T/V	0.1261	likely_benign	0.1144	benign	-0.425	Destabilizing	0.994	D	0.365	neutral	None	None	None	None	N
T/W	0.7167	likely_pathogenic	0.6549	pathogenic	-0.864	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
T/Y	0.4514	ambiguous	0.3981	ambiguous	-0.646	Destabilizing	1.0	D	0.702	prob.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.