TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27863	83812;83813;83814	chr2:178562545;178562544;178562543	chr2:179427272;179427271;179427270
N2AB	26222	78889;78890;78891	chr2:178562545;178562544;178562543	chr2:179427272;179427271;179427270
N2A	25295	76108;76109;76110	chr2:178562545;178562544;178562543	chr2:179427272;179427271;179427270
N2B	18798	56617;56618;56619	chr2:178562545;178562544;178562543	chr2:179427272;179427271;179427270
Novex-1	18923	56992;56993;56994	chr2:178562545;178562544;178562543	chr2:179427272;179427271;179427270
Novex-2	18990	57193;57194;57195	chr2:178562545;178562544;178562543	chr2:179427272;179427271;179427270
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-91
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.4526
• 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
P/R	None	None	0.664	N	0.389	0.221	0.353125101423	gnomAD-4.0.0	6.85921E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00458E-07	0	0
P/S	rs768816071	-0.361	0.22	N	0.41	0.155	0.215109475489	gnomAD-2.1.1	8.17E-06	None	None	None	None	N	None	0	0	None	0	1.12701E-04	None	0	None	0	0	0
P/S	rs768816071	-0.361	0.22	N	0.41	0.155	0.215109475489	gnomAD-4.0.0	4.11501E-06	None	None	None	None	N	None	0	0	None	0	1.00954E-04	None	0	0	9.00448E-07	0	1.66008E-05

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
P/A	0.0716	likely_benign	0.0698	benign	-0.72	Destabilizing	0.001	N	0.056	neutral	N	0.505776076	None	None	N
P/C	0.3755	ambiguous	0.3992	ambiguous	-0.666	Destabilizing	0.984	D	0.376	neutral	None	None	None	None	N
P/D	0.7326	likely_pathogenic	0.7422	pathogenic	-0.371	Destabilizing	0.428	N	0.491	neutral	None	None	None	None	N
P/E	0.3936	ambiguous	0.4189	ambiguous	-0.485	Destabilizing	0.428	N	0.51	neutral	None	None	None	None	N
P/F	0.4848	ambiguous	0.5101	ambiguous	-0.972	Destabilizing	0.568	D	0.445	neutral	None	None	None	None	N
P/G	0.4488	ambiguous	0.4277	ambiguous	-0.866	Destabilizing	0.272	N	0.361	neutral	None	None	None	None	N
P/H	0.2685	likely_benign	0.2944	benign	-0.408	Destabilizing	0.842	D	0.339	neutral	None	None	None	None	N
P/I	0.1589	likely_benign	0.1815	benign	-0.48	Destabilizing	0.568	D	0.428	neutral	None	None	None	None	N
P/K	0.2686	likely_benign	0.2884	benign	-0.406	Destabilizing	0.428	N	0.505	neutral	None	None	None	None	N
P/L	0.1064	likely_benign	0.1178	benign	-0.48	Destabilizing	0.22	N	0.432	neutral	N	0.461121207	None	None	N
P/M	0.2098	likely_benign	0.2273	benign	-0.31	Destabilizing	0.953	D	0.332	neutral	None	None	None	None	N
P/N	0.4277	ambiguous	0.4536	ambiguous	-0.132	Destabilizing	0.724	D	0.395	neutral	None	None	None	None	N
P/Q	0.1639	likely_benign	0.1802	benign	-0.439	Destabilizing	0.8	D	0.441	neutral	N	0.48914019	None	None	N
P/R	0.1988	likely_benign	0.2201	benign	0.135	Stabilizing	0.664	D	0.389	neutral	N	0.488539897	None	None	N
P/S	0.1551	likely_benign	0.156	benign	-0.561	Destabilizing	0.22	N	0.41	neutral	N	0.484999134	None	None	N
P/T	0.1075	likely_benign	0.1117	benign	-0.576	Destabilizing	0.002	N	0.13	neutral	N	0.482276882	None	None	N
P/V	0.1104	likely_benign	0.121	benign	-0.525	Destabilizing	0.272	N	0.365	neutral	None	None	None	None	N
P/W	0.7524	likely_pathogenic	0.7805	pathogenic	-0.999	Destabilizing	0.984	D	0.405	neutral	None	None	None	None	N
P/Y	0.4709	ambiguous	0.5105	ambiguous	-0.687	Destabilizing	0.023	N	0.297	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.