TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15901	47926;47927;47928	chr2:178617384;178617383;178617382	chr2:179482111;179482110;179482109
N2AB	14260	43003;43004;43005	chr2:178617384;178617383;178617382	chr2:179482111;179482110;179482109
N2A	13333	40222;40223;40224	chr2:178617384;178617383;178617382	chr2:179482111;179482110;179482109
N2B	6836	20731;20732;20733	chr2:178617384;178617383;178617382	chr2:179482111;179482110;179482109
Novex-1	6961	21106;21107;21108	chr2:178617384;178617383;178617382	chr2:179482111;179482110;179482109
Novex-2	7028	21307;21308;21309	chr2:178617384;178617383;178617382	chr2:179482111;179482110;179482109
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-3
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.3064
• 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
E/K	rs530338718	-0.244	0.978	N	0.513	0.311	0.371903410333	gnomAD-2.1.1	4.62E-06	None	None	None	None	N	None	0	3.48E-05	None	0	0	None	0	None	0	0	0
E/K	rs530338718	-0.244	0.978	N	0.513	0.311	0.371903410333	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.57E-05	0	0	0	None	0	0	0	0	0
E/K	rs530338718	-0.244	0.978	N	0.513	0.311	0.371903410333	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
E/K	rs530338718	-0.244	0.978	N	0.513	0.311	0.371903410333	gnomAD-4.0.0	2.51869E-06	None	None	None	None	N	None	0	3.67188E-05	None	0	0	None	0	0	1.70922E-06	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
E/A	0.1206	likely_benign	0.1138	benign	-0.7	Destabilizing	0.989	D	0.531	neutral	N	0.473589396	None	None	N
E/C	0.8648	likely_pathogenic	0.8508	pathogenic	-0.417	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
E/D	0.1566	likely_benign	0.1553	benign	-0.873	Destabilizing	0.104	N	0.237	neutral	N	0.451456569	None	None	N
E/F	0.7695	likely_pathogenic	0.7537	pathogenic	-0.224	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
E/G	0.223	likely_benign	0.2013	benign	-1.014	Destabilizing	0.994	D	0.579	neutral	N	0.478198163	None	None	N
E/H	0.5818	likely_pathogenic	0.5786	pathogenic	-0.318	Destabilizing	1.0	D	0.463	neutral	None	None	None	None	N
E/I	0.2946	likely_benign	0.2965	benign	0.139	Stabilizing	1.0	D	0.674	neutral	None	None	None	None	N
E/K	0.2171	likely_benign	0.2109	benign	-0.427	Destabilizing	0.978	D	0.513	neutral	N	0.460355969	None	None	N
E/L	0.406	ambiguous	0.3895	ambiguous	0.139	Stabilizing	0.999	D	0.653	neutral	None	None	None	None	N
E/M	0.4428	ambiguous	0.4323	ambiguous	0.378	Stabilizing	1.0	D	0.655	neutral	None	None	None	None	N
E/N	0.3349	likely_benign	0.3333	benign	-0.853	Destabilizing	0.998	D	0.47	neutral	None	None	None	None	N
E/P	0.5696	likely_pathogenic	0.5621	ambiguous	-0.119	Destabilizing	1.0	D	0.535	neutral	None	None	None	None	N
E/Q	0.2149	likely_benign	0.2087	benign	-0.746	Destabilizing	0.889	D	0.226	neutral	N	0.482459585	None	None	N
E/R	0.3908	ambiguous	0.3783	ambiguous	-0.098	Destabilizing	0.998	D	0.475	neutral	None	None	None	None	N
E/S	0.2358	likely_benign	0.2311	benign	-1.086	Destabilizing	0.992	D	0.485	neutral	None	None	None	None	N
E/T	0.2585	likely_benign	0.2594	benign	-0.834	Destabilizing	0.999	D	0.491	neutral	None	None	None	None	N
E/V	0.1621	likely_benign	0.1599	benign	-0.119	Destabilizing	0.998	D	0.615	neutral	N	0.469215362	None	None	N
E/W	0.9094	likely_pathogenic	0.9009	pathogenic	0.008	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
E/Y	0.6227	likely_pathogenic	0.6028	pathogenic	0.012	Stabilizing	1.0	D	0.647	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.