TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5654	17185;17186;17187	chr2:178731915;178731914;178731913	chr2:179596642;179596641;179596640
N2AB	5337	16234;16235;16236	chr2:178731915;178731914;178731913	chr2:179596642;179596641;179596640
N2A	4410	13453;13454;13455	chr2:178731915;178731914;178731913	chr2:179596642;179596641;179596640
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-40
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.1273
• 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
V/A	None	None	0.219	N	0.271	0.167	0.395595088485	gnomAD-4.0.0	1.59161E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85884E-06	0	0
V/G	rs763581306	-2.867	0.98	N	0.747	0.314	0.801125762009	gnomAD-2.1.1	4.03E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-05	0
V/G	rs763581306	-2.867	0.98	N	0.747	0.314	0.801125762009	gnomAD-4.0.0	3.02406E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.57415E-05	0	9.07331E-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
V/A	0.2688	likely_benign	0.2577	benign	-2.166	Highly Destabilizing	0.219	N	0.271	neutral	N	0.437836144	None	None	N
V/C	0.8391	likely_pathogenic	0.8016	pathogenic	-1.607	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
V/D	0.898	likely_pathogenic	0.8946	pathogenic	-2.66	Highly Destabilizing	0.997	D	0.821	deleterious	N	0.497201132	None	None	N
V/E	0.8246	likely_pathogenic	0.8223	pathogenic	-2.443	Highly Destabilizing	0.998	D	0.781	deleterious	None	None	None	None	N
V/F	0.4222	ambiguous	0.4271	ambiguous	-1.35	Destabilizing	0.994	D	0.811	deleterious	N	0.469182149	None	None	N
V/G	0.5121	ambiguous	0.4881	ambiguous	-2.701	Highly Destabilizing	0.98	D	0.747	deleterious	N	0.478589898	None	None	N
V/H	0.9403	likely_pathogenic	0.9411	pathogenic	-2.372	Highly Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
V/I	0.0853	likely_benign	0.0911	benign	-0.669	Destabilizing	0.911	D	0.593	neutral	N	0.504138494	None	None	N
V/K	0.8754	likely_pathogenic	0.8734	pathogenic	-1.892	Destabilizing	0.998	D	0.775	deleterious	None	None	None	None	N
V/L	0.3365	likely_benign	0.3391	benign	-0.669	Destabilizing	0.911	D	0.53	neutral	N	0.465041388	None	None	N
V/M	0.2159	likely_benign	0.2323	benign	-0.603	Destabilizing	0.931	D	0.478	neutral	None	None	None	None	N
V/N	0.7849	likely_pathogenic	0.7892	pathogenic	-2.153	Highly Destabilizing	0.999	D	0.814	deleterious	None	None	None	None	N
V/P	0.9714	likely_pathogenic	0.9698	pathogenic	-1.141	Destabilizing	0.998	D	0.8	deleterious	None	None	None	None	N
V/Q	0.8389	likely_pathogenic	0.8358	pathogenic	-2.014	Highly Destabilizing	0.998	D	0.78	deleterious	None	None	None	None	N
V/R	0.8476	likely_pathogenic	0.8392	pathogenic	-1.696	Destabilizing	0.998	D	0.819	deleterious	None	None	None	None	N
V/S	0.5556	ambiguous	0.5397	ambiguous	-2.775	Highly Destabilizing	0.971	D	0.731	prob.delet.	None	None	None	None	N
V/T	0.3148	likely_benign	0.322	benign	-2.407	Highly Destabilizing	0.985	D	0.634	neutral	None	None	None	None	N
V/W	0.9764	likely_pathogenic	0.9736	pathogenic	-1.82	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
V/Y	0.8837	likely_pathogenic	0.8734	pathogenic	-1.446	Destabilizing	0.999	D	0.775	deleterious	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.