TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3208	9847;9848;9849	chr2:178766462;178766461;178766460	chr2:179631189;179631188;179631187
N2AB	3208	9847;9848;9849	chr2:178766462;178766461;178766460	chr2:179631189;179631188;179631187
N2A	3208	9847;9848;9849	chr2:178766462;178766461;178766460	chr2:179631189;179631188;179631187
N2B	3162	9709;9710;9711	chr2:178766462;178766461;178766460	chr2:179631189;179631188;179631187
Novex-1	3162	9709;9710;9711	chr2:178766462;178766461;178766460	chr2:179631189;179631188;179631187
Novex-2	3162	9709;9710;9711	chr2:178766462;178766461;178766460	chr2:179631189;179631188;179631187
Novex-3	3208	9847;9848;9849	chr2:178766462;178766461;178766460	chr2:179631189;179631188;179631187

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-22
• Domain position: 62
• Structural Position: 141
• Q(SASA): 0.2587
• 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
S/C	None	None	0.99	N	0.459	0.39	0.534572409765	gnomAD-4.0.0	1.59053E-06	None	None	None	None	N	None	0	2.28634E-05	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
S/A	0.0875	likely_benign	0.088	benign	-0.642	Destabilizing	0.002	N	0.125	neutral	N	0.484837895	None	None	N
S/C	0.1971	likely_benign	0.2331	benign	-0.517	Destabilizing	0.99	D	0.459	neutral	N	0.50675312	None	None	N
S/D	0.4561	ambiguous	0.4779	ambiguous	-0.264	Destabilizing	0.617	D	0.444	neutral	None	None	None	None	N
S/E	0.5624	ambiguous	0.5724	pathogenic	-0.306	Destabilizing	0.617	D	0.402	neutral	None	None	None	None	N
S/F	0.2574	likely_benign	0.3212	benign	-0.922	Destabilizing	0.004	N	0.356	neutral	N	0.502132152	None	None	N
S/G	0.1455	likely_benign	0.1507	benign	-0.838	Destabilizing	0.25	N	0.406	neutral	None	None	None	None	N
S/H	0.4517	ambiguous	0.4761	ambiguous	-1.305	Destabilizing	0.972	D	0.465	neutral	None	None	None	None	N
S/I	0.2932	likely_benign	0.33	benign	-0.236	Destabilizing	0.447	N	0.433	neutral	None	None	None	None	N
S/K	0.7857	likely_pathogenic	0.8268	pathogenic	-0.671	Destabilizing	0.617	D	0.406	neutral	None	None	None	None	N
S/L	0.1172	likely_benign	0.1305	benign	-0.236	Destabilizing	0.25	N	0.419	neutral	None	None	None	None	N
S/M	0.2717	likely_benign	0.2728	benign	0.091	Stabilizing	0.92	D	0.478	neutral	None	None	None	None	N
S/N	0.1949	likely_benign	0.1835	benign	-0.511	Destabilizing	0.617	D	0.463	neutral	None	None	None	None	N
S/P	0.2676	likely_benign	0.3173	benign	-0.34	Destabilizing	0.896	D	0.465	neutral	N	0.495601332	None	None	N
S/Q	0.6244	likely_pathogenic	0.6205	pathogenic	-0.793	Destabilizing	0.92	D	0.488	neutral	None	None	None	None	N
S/R	0.681	likely_pathogenic	0.7457	pathogenic	-0.453	Destabilizing	0.85	D	0.464	neutral	None	None	None	None	N
S/T	0.0865	likely_benign	0.0881	benign	-0.598	Destabilizing	0.002	N	0.121	neutral	N	0.468961264	None	None	N
S/V	0.2779	likely_benign	0.2976	benign	-0.34	Destabilizing	0.447	N	0.419	neutral	None	None	None	None	N
S/W	0.3604	ambiguous	0.4501	ambiguous	-0.845	Destabilizing	0.992	D	0.517	neutral	None	None	None	None	N
S/Y	0.2261	likely_benign	0.2874	benign	-0.6	Destabilizing	0.681	D	0.473	neutral	N	0.513508906	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.