TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25329	76210;76211;76212	chr2:178570147;178570146;178570145	chr2:179434874;179434873;179434872
N2AB	23688	71287;71288;71289	chr2:178570147;178570146;178570145	chr2:179434874;179434873;179434872
N2A	22761	68506;68507;68508	chr2:178570147;178570146;178570145	chr2:179434874;179434873;179434872
N2B	16264	49015;49016;49017	chr2:178570147;178570146;178570145	chr2:179434874;179434873;179434872
Novex-1	16389	49390;49391;49392	chr2:178570147;178570146;178570145	chr2:179434874;179434873;179434872
Novex-2	16456	49591;49592;49593	chr2:178570147;178570146;178570145	chr2:179434874;179434873;179434872
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-72
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.5755
• 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
A/T	None	None	0.007	N	0.071	0.086	0.152612264143	gnomAD-4.0.0	1.59182E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43299E-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
A/C	0.3095	likely_benign	0.4055	ambiguous	-0.821	Destabilizing	0.992	D	0.318	neutral	None	None	None	None	I
A/D	0.1366	likely_benign	0.1458	benign	-0.524	Destabilizing	0.447	N	0.381	neutral	None	None	None	None	I
A/E	0.1244	likely_benign	0.1254	benign	-0.679	Destabilizing	0.004	N	0.17	neutral	N	0.402193136	None	None	I
A/F	0.2033	likely_benign	0.25	benign	-0.914	Destabilizing	0.92	D	0.405	neutral	None	None	None	None	I
A/G	0.1054	likely_benign	0.1183	benign	-0.221	Destabilizing	0.201	N	0.241	neutral	N	0.495220727	None	None	I
A/H	0.2724	likely_benign	0.3318	benign	-0.213	Destabilizing	0.977	D	0.367	neutral	None	None	None	None	I
A/I	0.1059	likely_benign	0.131	benign	-0.395	Destabilizing	0.447	N	0.303	neutral	None	None	None	None	I
A/K	0.2045	likely_benign	0.2227	benign	-0.518	Destabilizing	0.447	N	0.304	neutral	None	None	None	None	I
A/L	0.0896	likely_benign	0.1065	benign	-0.395	Destabilizing	0.25	N	0.3	neutral	None	None	None	None	I
A/M	0.1342	likely_benign	0.159	benign	-0.517	Destabilizing	0.92	D	0.314	neutral	None	None	None	None	I
A/N	0.1268	likely_benign	0.1502	benign	-0.232	Destabilizing	0.447	N	0.414	neutral	None	None	None	None	I
A/P	0.124	likely_benign	0.1443	benign	-0.309	Destabilizing	0.896	D	0.343	neutral	N	0.481712712	None	None	I
A/Q	0.1759	likely_benign	0.1972	benign	-0.509	Destabilizing	0.739	D	0.335	neutral	None	None	None	None	I
A/R	0.2222	likely_benign	0.2406	benign	-0.074	Destabilizing	0.85	D	0.337	neutral	None	None	None	None	I
A/S	0.0796	likely_benign	0.0827	benign	-0.409	Destabilizing	0.007	N	0.069	neutral	N	0.465281822	None	None	I
A/T	0.0696	likely_benign	0.0731	benign	-0.491	Destabilizing	0.007	N	0.071	neutral	N	0.418778741	None	None	I
A/V	0.0724	likely_benign	0.0807	benign	-0.309	Destabilizing	0.007	N	0.076	neutral	N	0.452219311	None	None	I
A/W	0.5299	ambiguous	0.6075	pathogenic	-1.014	Destabilizing	0.992	D	0.445	neutral	None	None	None	None	I
A/Y	0.2904	likely_benign	0.3678	ambiguous	-0.688	Destabilizing	0.972	D	0.398	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.