TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8483	25672;25673;25674	chr2:178717287;178717286;178717285	chr2:179582014;179582013;179582012
N2AB	8166	24721;24722;24723	chr2:178717287;178717286;178717285	chr2:179582014;179582013;179582012
N2A	7239	21940;21941;21942	chr2:178717287;178717286;178717285	chr2:179582014;179582013;179582012
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-70
• Domain position: 28
• Structural Position: 42
• Q(SASA): 0.3104
• 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/T	rs1156463241	-0.564	0.001	N	0.25	0.268	0.158396225186	gnomAD-2.1.1	3.18E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
A/T	rs1156463241	-0.564	0.001	N	0.25	0.268	0.158396225186	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
A/T	rs1156463241	-0.564	0.001	N	0.25	0.268	0.158396225186	gnomAD-4.0.0	3.09871E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.23837E-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
A/C	0.6361	likely_pathogenic	0.5379	ambiguous	-0.905	Destabilizing	0.983	D	0.575	neutral	None	None	None	None	I
A/D	0.1995	likely_benign	0.1855	benign	-0.519	Destabilizing	0.002	N	0.252	neutral	None	None	None	None	I
A/E	0.142	likely_benign	0.1379	benign	-0.655	Destabilizing	0.272	N	0.501	neutral	N	0.46941071	None	None	I
A/F	0.277	likely_benign	0.2414	benign	-0.853	Destabilizing	0.903	D	0.617	neutral	None	None	None	None	I
A/G	0.1439	likely_benign	0.1302	benign	-0.318	Destabilizing	0.021	N	0.444	neutral	N	0.517721945	None	None	I
A/H	0.3825	ambiguous	0.3227	benign	-0.228	Destabilizing	0.95	D	0.617	neutral	None	None	None	None	I
A/I	0.2005	likely_benign	0.1629	benign	-0.376	Destabilizing	0.57	D	0.567	neutral	None	None	None	None	I
A/K	0.2778	likely_benign	0.2344	benign	-0.67	Destabilizing	0.57	D	0.573	neutral	None	None	None	None	I
A/L	0.131	likely_benign	0.1169	benign	-0.376	Destabilizing	0.158	N	0.459	neutral	None	None	None	None	I
A/M	0.1833	likely_benign	0.1614	benign	-0.625	Destabilizing	0.354	N	0.371	neutral	None	None	None	None	I
A/N	0.2072	likely_benign	0.1787	benign	-0.403	Destabilizing	0.077	N	0.641	neutral	None	None	None	None	I
A/P	0.1346	likely_benign	0.1294	benign	-0.316	Destabilizing	0.001	N	0.194	neutral	N	0.323119064	None	None	I
A/Q	0.2066	likely_benign	0.1859	benign	-0.638	Destabilizing	0.076	N	0.257	neutral	None	None	None	None	I
A/R	0.2809	likely_benign	0.2389	benign	-0.226	Destabilizing	0.823	D	0.649	neutral	None	None	None	None	I
A/S	0.0783	likely_benign	0.0771	benign	-0.604	Destabilizing	0.008	N	0.46	neutral	N	0.485996316	None	None	I
A/T	0.08	likely_benign	0.0735	benign	-0.659	Destabilizing	0.001	N	0.25	neutral	N	0.492885003	None	None	I
A/V	0.1026	likely_benign	0.0894	benign	-0.316	Destabilizing	0.01	N	0.23	neutral	N	0.490403271	None	None	I
A/W	0.6641	likely_pathogenic	0.6059	pathogenic	-0.972	Destabilizing	0.995	D	0.648	neutral	None	None	None	None	I
A/Y	0.3916	ambiguous	0.3377	benign	-0.653	Destabilizing	0.95	D	0.618	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.