TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24587	73984;73985;73986	chr2:178572373;178572372;178572371	chr2:179437100;179437099;179437098
N2AB	22946	69061;69062;69063	chr2:178572373;178572372;178572371	chr2:179437100;179437099;179437098
N2A	22019	66280;66281;66282	chr2:178572373;178572372;178572371	chr2:179437100;179437099;179437098
N2B	15522	46789;46790;46791	chr2:178572373;178572372;178572371	chr2:179437100;179437099;179437098
Novex-1	15647	47164;47165;47166	chr2:178572373;178572372;178572371	chr2:179437100;179437099;179437098
Novex-2	15714	47365;47366;47367	chr2:178572373;178572372;178572371	chr2:179437100;179437099;179437098
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-66
• Domain position: 69
• Structural Position: 102
• Q(SASA): 0.1394
• 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
C/F	rs1326848733	None	0.964	N	0.471	0.266	0.706567288939	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
C/F	rs1326848733	None	0.964	N	0.471	0.266	0.706567288939	gnomAD-4.0.0	6.57307E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47059E-05	0	0
C/R	rs776113871	-0.324	0.656	N	0.373	0.216	0.53911333632	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	1.16077E-04	None	0	0	None	0	None	0	0	0
C/R	rs776113871	-0.324	0.656	N	0.373	0.216	0.53911333632	gnomAD-4.0.0	4.1073E-06	None	None	None	None	N	None	0	8.94935E-05	None	0	0	None	0	0	8.99871E-07	0	1.65733E-05
C/S	rs776113871	-0.914	0.001	N	0.149	0.149	0.515259903717	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
C/S	rs776113871	-0.914	0.001	N	0.149	0.149	0.515259903717	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
C/S	rs776113871	-0.914	0.001	N	0.149	0.149	0.515259903717	gnomAD-4.0.0	6.57289E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47046E-05	0	0
C/Y	rs1326848733	None	0.988	N	0.468	0.274	0.714984421374	gnomAD-4.0.0	6.84571E-07	None	None	None	None	N	None	0	0	None	0	2.52729E-05	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
C/A	0.4114	ambiguous	0.336	benign	-1.702	Destabilizing	0.008	N	0.065	neutral	None	None	None	None	N
C/D	0.8874	likely_pathogenic	0.7933	pathogenic	-0.032	Destabilizing	0.239	N	0.382	neutral	None	None	None	None	N
C/E	0.9294	likely_pathogenic	0.868	pathogenic	0.037	Stabilizing	0.281	N	0.324	neutral	None	None	None	None	N
C/F	0.3254	likely_benign	0.2337	benign	-1.168	Destabilizing	0.964	D	0.471	neutral	N	0.472000668	None	None	N
C/G	0.2261	likely_benign	0.1697	benign	-1.975	Destabilizing	0.137	N	0.315	neutral	N	0.448869575	None	None	N
C/H	0.6997	likely_pathogenic	0.5621	ambiguous	-1.87	Destabilizing	0.931	D	0.473	neutral	None	None	None	None	N
C/I	0.609	likely_pathogenic	0.4962	ambiguous	-1.015	Destabilizing	0.835	D	0.45	neutral	None	None	None	None	N
C/K	0.9325	likely_pathogenic	0.8634	pathogenic	-0.754	Destabilizing	0.028	N	0.152	neutral	None	None	None	None	N
C/L	0.5889	likely_pathogenic	0.4675	ambiguous	-1.015	Destabilizing	0.676	D	0.337	neutral	None	None	None	None	N
C/M	0.6416	likely_pathogenic	0.5543	ambiguous	-0.219	Destabilizing	0.991	D	0.429	neutral	None	None	None	None	N
C/N	0.5075	ambiguous	0.3797	ambiguous	-0.634	Destabilizing	0.018	N	0.209	neutral	None	None	None	None	N
C/P	0.9908	likely_pathogenic	0.9853	pathogenic	-1.218	Destabilizing	0.56	D	0.491	neutral	None	None	None	None	N
C/Q	0.7634	likely_pathogenic	0.6386	pathogenic	-0.614	Destabilizing	0.654	D	0.491	neutral	None	None	None	None	N
C/R	0.7755	likely_pathogenic	0.636	pathogenic	-0.526	Destabilizing	0.656	D	0.373	neutral	N	0.429646309	None	None	N
C/S	0.2745	likely_benign	0.2025	benign	-1.225	Destabilizing	0.001	N	0.149	neutral	N	0.41490893	None	None	N
C/T	0.4878	ambiguous	0.387	ambiguous	-0.977	Destabilizing	0.218	N	0.335	neutral	None	None	None	None	N
C/V	0.4964	ambiguous	0.411	ambiguous	-1.218	Destabilizing	0.438	N	0.324	neutral	None	None	None	None	N
C/W	0.7761	likely_pathogenic	0.6586	pathogenic	-1.075	Destabilizing	0.997	D	0.437	neutral	N	0.472254157	None	None	N
C/Y	0.5216	ambiguous	0.3806	ambiguous	-1.082	Destabilizing	0.988	D	0.468	neutral	N	0.517190723	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.