TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23611	71056;71057;71058	chr2:178575301;178575300;178575299	chr2:179440028;179440027;179440026
N2AB	21970	66133;66134;66135	chr2:178575301;178575300;178575299	chr2:179440028;179440027;179440026
N2A	21043	63352;63353;63354	chr2:178575301;178575300;178575299	chr2:179440028;179440027;179440026
N2B	14546	43861;43862;43863	chr2:178575301;178575300;178575299	chr2:179440028;179440027;179440026
Novex-1	14671	44236;44237;44238	chr2:178575301;178575300;178575299	chr2:179440028;179440027;179440026
Novex-2	14738	44437;44438;44439	chr2:178575301;178575300;178575299	chr2:179440028;179440027;179440026
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCG
• RefSeq wild type template codon: CGC
• Domain: Fn3-59
• Domain position: 80
• Structural Position: 114
• Q(SASA): 0.5427
• 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
A/E	rs72646891	-0.395	0.922	N	0.49	0.297	0.439018943094	gnomAD-4.0.0	6.84362E-07	None	None	None	None	I	None	0	0	None	0	2.52972E-05	None	0	0	0	0	0
A/T	rs373765469	-0.202	0.929	N	0.393	0.163	None	gnomAD-2.1.1	5.64E-05	None	None	None	None	I	None	6.46E-05	2.9E-05	None	4.98405E-04	0	None	3.27E-05	None	0	5.34E-05	0
A/T	rs373765469	-0.202	0.929	N	0.393	0.163	None	gnomAD-3.1.2	3.94E-05	None	None	None	None	I	None	7.24E-05	0	0	2.88018E-04	0	None	0	0	2.94E-05	0	0
A/T	rs373765469	-0.202	0.929	N	0.393	0.163	None	gnomAD-4.0.0	4.15287E-05	None	None	None	None	I	None	4.00449E-05	1.66761E-05	None	4.0546E-04	0	None	0	0	3.89949E-05	2.19573E-05	4.80492E-05
A/V	rs72646891	-0.086	0.649	N	0.409	0.217	None	gnomAD-2.1.1	9.83717E-04	None	None	None	None	I	None	1.04597E-02	3.68209E-04	None	0	0	None	9.81E-05	None	0	3.91E-05	1.40726E-04
A/V	rs72646891	-0.086	0.649	N	0.409	0.217	None	gnomAD-3.1.2	2.97964E-03	None	None	None	None	I	None	1.05304E-02	7.20461E-04	0	0	1.93723E-04	None	0	0	4.41E-05	2.07039E-04	4.79386E-04
A/V	rs72646891	-0.086	0.649	N	0.409	0.217	None	1000 genomes	4.19329E-03	None	None	None	None	I	None	1.51E-02	0	None	None	0	1E-03	None	None	None	0	None
A/V	rs72646891	-0.086	0.649	N	0.409	0.217	None	gnomAD-4.0.0	5.78914E-04	None	None	None	None	I	None	1.0495E-02	5.50073E-04	None	0	6.71441E-05	None	0	1.65125E-04	5.25593E-05	6.5879E-05	6.72473E-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
A/C	0.3649	ambiguous	0.3977	ambiguous	-0.858	Destabilizing	0.998	D	0.433	neutral	None	None	None	None	I
A/D	0.6945	likely_pathogenic	0.7533	pathogenic	-0.413	Destabilizing	0.956	D	0.59	neutral	None	None	None	None	I
A/E	0.5314	ambiguous	0.6006	pathogenic	-0.563	Destabilizing	0.922	D	0.49	neutral	N	0.501549267	None	None	I
A/F	0.3091	likely_benign	0.363	ambiguous	-0.89	Destabilizing	0.956	D	0.661	neutral	None	None	None	None	I
A/G	0.2257	likely_benign	0.2368	benign	-0.212	Destabilizing	0.922	D	0.399	neutral	N	0.493295143	None	None	I
A/H	0.5472	ambiguous	0.5926	pathogenic	-0.175	Destabilizing	0.998	D	0.667	neutral	None	None	None	None	I
A/I	0.231	likely_benign	0.2818	benign	-0.412	Destabilizing	0.043	N	0.341	neutral	None	None	None	None	I
A/K	0.6189	likely_pathogenic	0.6924	pathogenic	-0.423	Destabilizing	0.86	D	0.485	neutral	None	None	None	None	I
A/L	0.2168	likely_benign	0.2543	benign	-0.412	Destabilizing	0.303	N	0.474	neutral	None	None	None	None	I
A/M	0.2262	likely_benign	0.2648	benign	-0.507	Destabilizing	0.956	D	0.523	neutral	None	None	None	None	I
A/N	0.4388	ambiguous	0.4725	ambiguous	-0.207	Destabilizing	0.956	D	0.606	neutral	None	None	None	None	I
A/P	0.8767	likely_pathogenic	0.9022	pathogenic	-0.322	Destabilizing	0.988	D	0.519	neutral	N	0.508960101	None	None	I
A/Q	0.46	ambiguous	0.4999	ambiguous	-0.467	Destabilizing	0.978	D	0.517	neutral	None	None	None	None	I
A/R	0.5207	ambiguous	0.5861	pathogenic	-0.006	Destabilizing	0.978	D	0.522	neutral	None	None	None	None	I
A/S	0.1102	likely_benign	0.1159	benign	-0.403	Destabilizing	0.161	N	0.183	neutral	N	0.479597914	None	None	I
A/T	0.1028	likely_benign	0.1228	benign	-0.478	Destabilizing	0.929	D	0.393	neutral	N	0.470091791	None	None	I
A/V	0.1088	likely_benign	0.1276	benign	-0.322	Destabilizing	0.649	D	0.409	neutral	N	0.442290319	None	None	I
A/W	0.7784	likely_pathogenic	0.8285	pathogenic	-0.975	Destabilizing	0.998	D	0.74	deleterious	None	None	None	None	I
A/Y	0.527	ambiguous	0.5859	pathogenic	-0.657	Destabilizing	0.978	D	0.665	neutral	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.