TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25720	77383;77384;77385	chr2:178568974;178568973;178568972	chr2:179433701;179433700;179433699
N2AB	24079	72460;72461;72462	chr2:178568974;178568973;178568972	chr2:179433701;179433700;179433699
N2A	23152	69679;69680;69681	chr2:178568974;178568973;178568972	chr2:179433701;179433700;179433699
N2B	16655	50188;50189;50190	chr2:178568974;178568973;178568972	chr2:179433701;179433700;179433699
Novex-1	16780	50563;50564;50565	chr2:178568974;178568973;178568972	chr2:179433701;179433700;179433699
Novex-2	16847	50764;50765;50766	chr2:178568974;178568973;178568972	chr2:179433701;179433700;179433699
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: Fn3-75
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.568
• 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	rs748079783	-0.714	None	N	0.176	0.12	0.162503812791	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	8.89E-06	0
T/A	rs748079783	-0.714	None	N	0.176	0.12	0.162503812791	gnomAD-4.0.0	2.05306E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79923E-06	1.15969E-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	0.0692	likely_benign	0.0727	benign	-0.832	Destabilizing	None	N	0.176	neutral	N	0.490180267	None	None	N
T/C	0.338	likely_benign	0.3478	ambiguous	-0.544	Destabilizing	0.951	D	0.522	neutral	None	None	None	None	N
T/D	0.2676	likely_benign	0.2679	benign	-0.149	Destabilizing	0.129	N	0.394	neutral	None	None	None	None	N
T/E	0.1647	likely_benign	0.1618	benign	-0.106	Destabilizing	None	N	0.266	neutral	None	None	None	None	N
T/F	0.25	likely_benign	0.2449	benign	-0.826	Destabilizing	0.836	D	0.549	neutral	None	None	None	None	N
T/G	0.1631	likely_benign	0.1667	benign	-1.128	Destabilizing	0.129	N	0.393	neutral	None	None	None	None	N
T/H	0.2577	likely_benign	0.2514	benign	-1.344	Destabilizing	0.836	D	0.535	neutral	None	None	None	None	N
T/I	0.1429	likely_benign	0.1369	benign	-0.124	Destabilizing	0.351	N	0.553	neutral	N	0.504976361	None	None	N
T/K	0.1991	likely_benign	0.1911	benign	-0.693	Destabilizing	0.101	N	0.397	neutral	N	0.462145516	None	None	N
T/L	0.074	likely_benign	0.0715	benign	-0.124	Destabilizing	0.129	N	0.403	neutral	None	None	None	None	N
T/M	0.0723	likely_benign	0.0711	benign	0.004	Stabilizing	0.94	D	0.537	neutral	None	None	None	None	N
T/N	0.0917	likely_benign	0.0909	benign	-0.783	Destabilizing	0.418	N	0.341	neutral	None	None	None	None	N
T/P	0.1966	likely_benign	0.174	benign	-0.326	Destabilizing	0.523	D	0.542	neutral	N	0.508651384	None	None	N
T/Q	0.153	likely_benign	0.1526	benign	-0.815	Destabilizing	0.264	N	0.466	neutral	None	None	None	None	N
T/R	0.1944	likely_benign	0.1833	benign	-0.561	Destabilizing	0.351	N	0.466	neutral	N	0.482195502	None	None	N
T/S	0.0902	likely_benign	0.0917	benign	-1.071	Destabilizing	0.101	N	0.271	neutral	N	0.471149002	None	None	N
T/V	0.1035	likely_benign	0.103	benign	-0.326	Destabilizing	0.129	N	0.331	neutral	None	None	None	None	N
T/W	0.5786	likely_pathogenic	0.562	ambiguous	-0.812	Destabilizing	0.983	D	0.551	neutral	None	None	None	None	N
T/Y	0.2896	likely_benign	0.2832	benign	-0.551	Destabilizing	0.94	D	0.551	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.