TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29918	89977;89978;89979	chr2:178553148;178553147;178553146	chr2:179417875;179417874;179417873
N2AB	28277	85054;85055;85056	chr2:178553148;178553147;178553146	chr2:179417875;179417874;179417873
N2A	27350	82273;82274;82275	chr2:178553148;178553147;178553146	chr2:179417875;179417874;179417873
N2B	20853	62782;62783;62784	chr2:178553148;178553147;178553146	chr2:179417875;179417874;179417873
Novex-1	20978	63157;63158;63159	chr2:178553148;178553147;178553146	chr2:179417875;179417874;179417873
Novex-2	21045	63358;63359;63360	chr2:178553148;178553147;178553146	chr2:179417875;179417874;179417873
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-147
• Domain position: 77
• Structural Position: 163
• Q(SASA): 0.8359
• Predicted PPI site: I

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	rs768749427	-0.122	0.999	N	0.598	0.413	0.489658423131	gnomAD-2.1.1	3.22E-05	None	None	None	None	I	None	0	2.32045E-04	None	0	0	None	0	None	0	0	0
V/A	rs768749427	-0.122	0.999	N	0.598	0.413	0.489658423131	gnomAD-4.0.0	1.91213E-05	None	None	None	None	I	None	0	2.74461E-04	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
V/A	0.1825	likely_benign	0.1698	benign	-0.324	Destabilizing	0.999	D	0.598	neutral	N	0.396473177	None	None	I
V/C	0.7399	likely_pathogenic	0.7167	pathogenic	-0.745	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
V/D	0.6922	likely_pathogenic	0.6432	pathogenic	-0.198	Destabilizing	1.0	D	0.745	deleterious	D	0.535254487	None	None	I
V/E	0.5655	likely_pathogenic	0.5327	ambiguous	-0.32	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	I
V/F	0.2523	likely_benign	0.2225	benign	-0.719	Destabilizing	1.0	D	0.721	prob.delet.	N	0.490692847	None	None	I
V/G	0.3758	ambiguous	0.348	ambiguous	-0.385	Destabilizing	1.0	D	0.723	prob.delet.	N	0.510606759	None	None	I
V/H	0.7757	likely_pathogenic	0.745	pathogenic	-0.061	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	I
V/I	0.0924	likely_benign	0.0881	benign	-0.312	Destabilizing	0.997	D	0.549	neutral	N	0.483054798	None	None	I
V/K	0.6634	likely_pathogenic	0.6146	pathogenic	-0.305	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
V/L	0.4101	ambiguous	0.3685	ambiguous	-0.312	Destabilizing	0.997	D	0.62	neutral	N	0.468989423	None	None	I
V/M	0.2482	likely_benign	0.2225	benign	-0.466	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
V/N	0.5026	ambiguous	0.4767	ambiguous	-0.112	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
V/P	0.8653	likely_pathogenic	0.8221	pathogenic	-0.287	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	I
V/Q	0.5781	likely_pathogenic	0.5509	ambiguous	-0.326	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
V/R	0.6149	likely_pathogenic	0.5553	ambiguous	0.12	Stabilizing	1.0	D	0.752	deleterious	None	None	None	None	I
V/S	0.2789	likely_benign	0.2733	benign	-0.429	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
V/T	0.2218	likely_benign	0.1999	benign	-0.457	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	I
V/W	0.9115	likely_pathogenic	0.8879	pathogenic	-0.783	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
V/Y	0.7402	likely_pathogenic	0.6872	pathogenic	-0.492	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I

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.