TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18519	55780;55781;55782	chr2:178601442;178601441;178601440	chr2:179466169;179466168;179466167
N2AB	16878	50857;50858;50859	chr2:178601442;178601441;178601440	chr2:179466169;179466168;179466167
N2A	15951	48076;48077;48078	chr2:178601442;178601441;178601440	chr2:179466169;179466168;179466167
N2B	9454	28585;28586;28587	chr2:178601442;178601441;178601440	chr2:179466169;179466168;179466167
Novex-1	9579	28960;28961;28962	chr2:178601442;178601441;178601440	chr2:179466169;179466168;179466167
Novex-2	9646	29161;29162;29163	chr2:178601442;178601441;178601440	chr2:179466169;179466168;179466167
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Fn3-22
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.07
• 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
R/K	None	None	None	N	0.148	0.168	0.107399877778	gnomAD-4.0.0	1.36906E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79955E-06	0	0
R/T	None	None	0.117	N	0.454	0.13	0.200317383148	gnomAD-4.0.0	6.84529E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99776E-07	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
R/A	0.8925	likely_pathogenic	0.9453	pathogenic	-2.209	Highly Destabilizing	0.035	N	0.454	neutral	None	None	None	None	N
R/C	0.4738	ambiguous	0.6125	pathogenic	-2.035	Highly Destabilizing	0.935	D	0.659	neutral	None	None	None	None	N
R/D	0.9847	likely_pathogenic	0.9931	pathogenic	-0.647	Destabilizing	0.149	N	0.553	neutral	None	None	None	None	N
R/E	0.8697	likely_pathogenic	0.9353	pathogenic	-0.443	Destabilizing	0.035	N	0.46	neutral	None	None	None	None	N
R/F	0.9048	likely_pathogenic	0.9715	pathogenic	-1.618	Destabilizing	0.791	D	0.651	neutral	None	None	None	None	N
R/G	0.8369	likely_pathogenic	0.9214	pathogenic	-2.546	Highly Destabilizing	0.117	N	0.515	neutral	N	0.469473135	None	None	N
R/H	0.3581	ambiguous	0.4816	ambiguous	-2.26	Highly Destabilizing	0.555	D	0.441	neutral	None	None	None	None	N
R/I	0.8336	likely_pathogenic	0.9101	pathogenic	-1.23	Destabilizing	0.555	D	0.636	neutral	None	None	None	None	N
R/K	0.0918	likely_benign	0.1218	benign	-1.335	Destabilizing	None	N	0.148	neutral	N	0.405214798	None	None	N
R/L	0.7	likely_pathogenic	0.8255	pathogenic	-1.23	Destabilizing	0.149	N	0.515	neutral	None	None	None	None	N
R/M	0.6773	likely_pathogenic	0.8144	pathogenic	-1.596	Destabilizing	0.741	D	0.516	neutral	D	0.525602349	None	None	N
R/N	0.9412	likely_pathogenic	0.9726	pathogenic	-1.151	Destabilizing	0.149	N	0.432	neutral	None	None	None	None	N
R/P	0.995	likely_pathogenic	0.9968	pathogenic	-1.545	Destabilizing	0.555	D	0.562	neutral	None	None	None	None	N
R/Q	0.281	likely_benign	0.3407	ambiguous	-1.203	Destabilizing	0.081	N	0.458	neutral	None	None	None	None	N
R/S	0.9449	likely_pathogenic	0.9779	pathogenic	-2.279	Highly Destabilizing	0.062	N	0.453	neutral	N	0.490948271	None	None	N
R/T	0.8739	likely_pathogenic	0.9387	pathogenic	-1.857	Destabilizing	0.117	N	0.454	neutral	N	0.515846715	None	None	N
R/V	0.8389	likely_pathogenic	0.9205	pathogenic	-1.545	Destabilizing	0.38	N	0.589	neutral	None	None	None	None	N
R/W	0.6919	likely_pathogenic	0.8437	pathogenic	-0.983	Destabilizing	0.915	D	0.691	prob.neutral	N	0.519540381	None	None	N
R/Y	0.7926	likely_pathogenic	0.9163	pathogenic	-0.875	Destabilizing	0.555	D	0.61	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.