TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9294	28105;28106;28107	chr2:178711950;178711949;178711948	chr2:179576677;179576676;179576675
N2AB	8977	27154;27155;27156	chr2:178711950;178711949;178711948	chr2:179576677;179576676;179576675
N2A	8050	24373;24374;24375	chr2:178711950;178711949;178711948	chr2:179576677;179576676;179576675
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: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-78
• Domain position: 90
• Structural Position: 177
• Q(SASA): 0.2316
• 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/F	None	None	1.0	D	0.908	0.759	0.926651531717	gnomAD-4.0.0	2.08206E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.72548E-06	0	0
V/I	rs368775401	-0.804	0.999	D	0.741	0.433	None	gnomAD-2.1.1	8.49E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.87E-05	0
V/I	rs368775401	-0.804	0.999	D	0.741	0.433	None	gnomAD-4.0.0	6.24617E-06	None	None	None	None	N	None	0	0	None	0	2.53088E-05	None	0	0	6.35946E-06	1.21919E-05	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	0.5976	likely_pathogenic	0.5796	pathogenic	-1.741	Destabilizing	0.999	D	0.78	deleterious	D	0.623393793	None	None	N
V/C	0.9541	likely_pathogenic	0.9533	pathogenic	-1.56	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
V/D	0.9889	likely_pathogenic	0.9917	pathogenic	-1.728	Destabilizing	1.0	D	0.898	deleterious	D	0.640018567	None	None	N
V/E	0.9673	likely_pathogenic	0.975	pathogenic	-1.673	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
V/F	0.7475	likely_pathogenic	0.8022	pathogenic	-1.282	Destabilizing	1.0	D	0.908	deleterious	D	0.639413154	None	None	N
V/G	0.8346	likely_pathogenic	0.8392	pathogenic	-2.092	Highly Destabilizing	1.0	D	0.884	deleterious	D	0.640018567	None	None	N
V/H	0.99	likely_pathogenic	0.9924	pathogenic	-1.54	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
V/I	0.0866	likely_benign	0.0984	benign	-0.844	Destabilizing	0.999	D	0.741	deleterious	D	0.536879001	None	None	N
V/K	0.9711	likely_pathogenic	0.9755	pathogenic	-1.292	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
V/L	0.5677	likely_pathogenic	0.6259	pathogenic	-0.844	Destabilizing	0.999	D	0.779	deleterious	D	0.605356389	None	None	N
V/M	0.5724	likely_pathogenic	0.6366	pathogenic	-0.939	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
V/N	0.9586	likely_pathogenic	0.9641	pathogenic	-1.252	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
V/P	0.9061	likely_pathogenic	0.9174	pathogenic	-1.112	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
V/Q	0.9641	likely_pathogenic	0.9693	pathogenic	-1.388	Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
V/R	0.9524	likely_pathogenic	0.9583	pathogenic	-0.887	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
V/S	0.8381	likely_pathogenic	0.8345	pathogenic	-1.862	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/T	0.726	likely_pathogenic	0.6699	pathogenic	-1.693	Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
V/W	0.9939	likely_pathogenic	0.9966	pathogenic	-1.46	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
V/Y	0.9763	likely_pathogenic	0.9822	pathogenic	-1.149	Destabilizing	1.0	D	0.912	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.