TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21597	65014;65015;65016	chr2:178584852;178584851;178584850	chr2:179449579;179449578;179449577
N2AB	19956	60091;60092;60093	chr2:178584852;178584851;178584850	chr2:179449579;179449578;179449577
N2A	19029	57310;57311;57312	chr2:178584852;178584851;178584850	chr2:179449579;179449578;179449577
N2B	12532	37819;37820;37821	chr2:178584852;178584851;178584850	chr2:179449579;179449578;179449577
Novex-1	12657	38194;38195;38196	chr2:178584852;178584851;178584850	chr2:179449579;179449578;179449577
Novex-2	12724	38395;38396;38397	chr2:178584852;178584851;178584850	chr2:179449579;179449578;179449577
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-44
• Domain position: 39
• Structural Position: 40
• Q(SASA): 0.1154
• 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	rs1374577570	-2.742	0.998	D	0.619	0.542	0.783386442946	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
V/A	rs1374577570	-2.742	0.998	D	0.619	0.542	0.783386442946	gnomAD-4.0.0	1.59207E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43299E-05	0
V/E	None	None	1.0	D	0.882	0.715	0.892875781192	gnomAD-4.0.0	1.59207E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85987E-06	0	0
V/L	rs150661999	-0.501	0.981	N	0.575	0.294	0.637308043038	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	0	0	0
V/L	rs150661999	-0.501	0.981	N	0.575	0.294	0.637308043038	gnomAD-4.0.0	6.8436E-07	None	None	None	None	N	None	0	0	None	0	2.52169E-05	None	0	0	0	0	0
V/M	rs150661999	-0.884	0.999	D	0.757	0.518	None	gnomAD-2.1.1	3.40481E-03	None	None	None	None	N	None	2.06748E-04	7.6392E-04	None	1.06527E-03	1.02912E-04	None	2.16993E-02	None	4E-05	1.73225E-03	2.95027E-03
V/M	rs150661999	-0.884	0.999	D	0.757	0.518	None	gnomAD-3.1.2	1.76969E-03	None	None	None	None	N	None	2.41453E-04	1.83655E-03	0	8.64553E-04	1.9425E-04	None	0	0	1.63322E-03	2.33664E-02	1.43403E-03
V/M	rs150661999	-0.884	0.999	D	0.757	0.518	None	1000 genomes	5.99042E-03	None	None	None	None	N	None	0	1.4E-03	None	None	0	2E-03	None	None	None	2.76E-02	None
V/M	rs150661999	-0.884	0.999	D	0.757	0.518	None	gnomAD-4.0.0	2.18863E-03	None	None	None	None	N	None	3.20085E-04	9.83792E-04	None	8.44994E-04	1.78603E-04	None	6.2502E-05	4.12814E-03	1.0801E-03	2.11906E-02	2.91443E-03

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	0.865	likely_pathogenic	0.8812	pathogenic	-2.44	Highly Destabilizing	0.998	D	0.619	neutral	D	0.550364803	None	None	N
V/C	0.9754	likely_pathogenic	0.9722	pathogenic	-1.995	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
V/D	0.9992	likely_pathogenic	0.9994	pathogenic	-3.483	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
V/E	0.9957	likely_pathogenic	0.9966	pathogenic	-3.153	Highly Destabilizing	1.0	D	0.882	deleterious	D	0.562646161	None	None	N
V/F	0.8868	likely_pathogenic	0.8956	pathogenic	-1.417	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
V/G	0.9718	likely_pathogenic	0.9781	pathogenic	-3.074	Highly Destabilizing	1.0	D	0.889	deleterious	D	0.562646161	None	None	N
V/H	0.9988	likely_pathogenic	0.999	pathogenic	-2.996	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
V/I	0.087	likely_benign	0.0835	benign	-0.592	Destabilizing	0.813	D	0.323	neutral	None	None	None	None	N
V/K	0.9965	likely_pathogenic	0.9973	pathogenic	-2.134	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
V/L	0.4719	ambiguous	0.483	ambiguous	-0.592	Destabilizing	0.981	D	0.575	neutral	N	0.484434881	None	None	N
V/M	0.6505	likely_pathogenic	0.6911	pathogenic	-0.847	Destabilizing	0.999	D	0.757	deleterious	D	0.539261987	None	None	N
V/N	0.9972	likely_pathogenic	0.998	pathogenic	-2.852	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
V/P	0.9952	likely_pathogenic	0.9965	pathogenic	-1.189	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
V/Q	0.9947	likely_pathogenic	0.9959	pathogenic	-2.474	Highly Destabilizing	1.0	D	0.918	deleterious	None	None	None	None	N
V/R	0.9931	likely_pathogenic	0.9943	pathogenic	-2.218	Highly Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	N
V/S	0.9832	likely_pathogenic	0.9878	pathogenic	-3.386	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/T	0.8951	likely_pathogenic	0.9164	pathogenic	-2.886	Highly Destabilizing	0.998	D	0.707	prob.neutral	None	None	None	None	N
V/W	0.998	likely_pathogenic	0.9981	pathogenic	-2.017	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/Y	0.9938	likely_pathogenic	0.9943	pathogenic	-1.672	Destabilizing	1.0	D	0.846	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.