TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21698	65317;65318;65319	chr2:178584459;178584458;178584457	chr2:179449186;179449185;179449184
N2AB	20057	60394;60395;60396	chr2:178584459;178584458;178584457	chr2:179449186;179449185;179449184
N2A	19130	57613;57614;57615	chr2:178584459;178584458;178584457	chr2:179449186;179449185;179449184
N2B	12633	38122;38123;38124	chr2:178584459;178584458;178584457	chr2:179449186;179449185;179449184
Novex-1	12758	38497;38498;38499	chr2:178584459;178584458;178584457	chr2:179449186;179449185;179449184
Novex-2	12825	38698;38699;38700	chr2:178584459;178584458;178584457	chr2:179449186;179449185;179449184
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Fn3-45
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.2638
• 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/C	rs72646861	-1.839	1.0	N	0.761	0.36	None	gnomAD-2.1.1	7.59038E-03	None	None	None	None	N	None	5.78847E-04	1.61455E-03	None	1.94504E-02	1.99648E-02	None	3.58567E-02	None	1.59898E-04	2.49577E-03	6.32733E-03
R/C	rs72646861	-1.839	1.0	N	0.761	0.36	None	gnomAD-3.1.2	3.48657E-03	None	None	None	None	N	None	4.58826E-04	1.44243E-03	4.38597E-03	1.84544E-02	1.98135E-02	None	4.71165E-04	6.32911E-03	2.03019E-03	3.41474E-02	4.31035E-03
R/C	rs72646861	-1.839	1.0	N	0.761	0.36	None	1000 genomes	1.29792E-02	None	None	None	None	N	None	8E-04	4.3E-03	None	None	2.28E-02	2E-03	None	None	None	3.68E-02	None
R/C	rs72646861	-1.839	1.0	N	0.761	0.36	None	gnomAD-4.0.0	4.37747E-03	None	None	None	None	N	None	5.20166E-04	1.66739E-03	None	1.96701E-02	1.56369E-02	None	2.49984E-04	1.56869E-02	1.62947E-03	3.51919E-02	6.40471E-03
R/H	rs371581072	-2.023	1.0	N	0.673	0.368	None	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
R/H	rs371581072	-2.023	1.0	N	0.673	0.368	None	gnomAD-4.0.0	2.25854E-05	None	None	None	None	N	None	0	2.23704E-05	None	0	2.52793E-05	None	0	0	2.33907E-05	4.638E-05	1.65717E-05
R/L	rs371581072	-0.835	0.996	N	0.729	0.355	None	gnomAD-2.1.1	3.93E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	7.04E-05	2.81294E-04
R/L	rs371581072	-0.835	0.996	N	0.729	0.355	None	gnomAD-3.1.2	5.92E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	8.83E-05	0	0
R/L	rs371581072	-0.835	0.996	N	0.729	0.355	None	gnomAD-4.0.0	1.15303E-04	None	None	None	None	N	None	4.0078E-05	0	None	0	0	None	0	0	1.47517E-04	0	1.44166E-04

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	0.9374	likely_pathogenic	0.9311	pathogenic	-2.027	Highly Destabilizing	0.985	D	0.703	prob.neutral	None	None	None	None	N
R/C	0.4177	ambiguous	0.3662	ambiguous	-1.991	Destabilizing	1.0	D	0.761	deleterious	N	0.477543622	None	None	N
R/D	0.9909	likely_pathogenic	0.9907	pathogenic	-1.287	Destabilizing	0.998	D	0.729	prob.delet.	None	None	None	None	N
R/E	0.8704	likely_pathogenic	0.8653	pathogenic	-1.032	Destabilizing	0.985	D	0.658	neutral	None	None	None	None	N
R/F	0.8926	likely_pathogenic	0.8842	pathogenic	-1.042	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
R/G	0.8957	likely_pathogenic	0.8829	pathogenic	-2.417	Highly Destabilizing	0.996	D	0.729	prob.delet.	N	0.488067461	None	None	N
R/H	0.3357	likely_benign	0.2856	benign	-1.803	Destabilizing	1.0	D	0.673	neutral	N	0.469709717	None	None	N
R/I	0.7569	likely_pathogenic	0.7734	pathogenic	-0.881	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
R/K	0.1727	likely_benign	0.1867	benign	-1.213	Destabilizing	0.271	N	0.305	neutral	None	None	None	None	N
R/L	0.7216	likely_pathogenic	0.717	pathogenic	-0.881	Destabilizing	0.996	D	0.729	prob.delet.	N	0.466667842	None	None	N
R/M	0.6758	likely_pathogenic	0.6887	pathogenic	-1.384	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
R/N	0.969	likely_pathogenic	0.967	pathogenic	-1.682	Destabilizing	0.998	D	0.647	neutral	None	None	None	None	N
R/P	0.9972	likely_pathogenic	0.9974	pathogenic	-1.253	Destabilizing	1.0	D	0.779	deleterious	N	0.514654412	None	None	N
R/Q	0.2494	likely_benign	0.2193	benign	-1.473	Destabilizing	0.996	D	0.657	neutral	None	None	None	None	N
R/S	0.9587	likely_pathogenic	0.9505	pathogenic	-2.555	Highly Destabilizing	0.992	D	0.682	prob.neutral	N	0.479825028	None	None	N
R/T	0.8611	likely_pathogenic	0.8517	pathogenic	-2.059	Highly Destabilizing	0.993	D	0.695	prob.neutral	None	None	None	None	N
R/V	0.8011	likely_pathogenic	0.7944	pathogenic	-1.253	Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
R/W	0.4747	ambiguous	0.4183	ambiguous	-0.497	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
R/Y	0.7024	likely_pathogenic	0.6632	pathogenic	-0.43	Destabilizing	0.999	D	0.783	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.