TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1864	5815;5816;5817	chr2:178776274;178776273;178776272	chr2:179641001;179641000;179640999
N2AB	1864	5815;5816;5817	chr2:178776274;178776273;178776272	chr2:179641001;179641000;179640999
N2A	1864	5815;5816;5817	chr2:178776274;178776273;178776272	chr2:179641001;179641000;179640999
N2B	1818	5677;5678;5679	chr2:178776274;178776273;178776272	chr2:179641001;179641000;179640999
Novex-1	1818	5677;5678;5679	chr2:178776274;178776273;178776272	chr2:179641001;179641000;179640999
Novex-2	1818	5677;5678;5679	chr2:178776274;178776273;178776272	chr2:179641001;179641000;179640999
Novex-3	1864	5815;5816;5817	chr2:178776274;178776273;178776272	chr2:179641001;179641000;179640999

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-9
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.2081
• 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
V/I	rs2092215067	None	0.997	N	0.535	0.375	0.638969403159	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-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	0.891	likely_pathogenic	0.8833	pathogenic	-1.96	Destabilizing	0.999	D	0.611	neutral	N	0.492029847	None	None	I
V/C	0.9759	likely_pathogenic	0.9773	pathogenic	-1.311	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
V/D	0.9987	likely_pathogenic	0.9991	pathogenic	-2.796	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
V/E	0.9945	likely_pathogenic	0.9961	pathogenic	-2.667	Highly Destabilizing	1.0	D	0.841	deleterious	D	0.671409924	None	None	I
V/F	0.9199	likely_pathogenic	0.9396	pathogenic	-1.186	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	I
V/G	0.9631	likely_pathogenic	0.966	pathogenic	-2.393	Highly Destabilizing	1.0	D	0.843	deleterious	D	0.65277814	None	None	I
V/H	0.9986	likely_pathogenic	0.9991	pathogenic	-2.221	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	I
V/I	0.1352	likely_benign	0.1495	benign	-0.775	Destabilizing	0.997	D	0.535	neutral	N	0.50228917	None	None	I
V/K	0.9972	likely_pathogenic	0.998	pathogenic	-1.668	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
V/L	0.7748	likely_pathogenic	0.8257	pathogenic	-0.775	Destabilizing	0.997	D	0.628	neutral	D	0.598212504	None	None	I
V/M	0.7965	likely_pathogenic	0.8433	pathogenic	-0.627	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
V/N	0.9957	likely_pathogenic	0.9966	pathogenic	-1.759	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	I
V/P	0.9958	likely_pathogenic	0.9964	pathogenic	-1.144	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	I
V/Q	0.9949	likely_pathogenic	0.9963	pathogenic	-1.736	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	I
V/R	0.9957	likely_pathogenic	0.9967	pathogenic	-1.342	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	I
V/S	0.9767	likely_pathogenic	0.9785	pathogenic	-2.221	Highly Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	I
V/T	0.9128	likely_pathogenic	0.9199	pathogenic	-1.991	Destabilizing	0.999	D	0.619	neutral	None	None	None	None	I
V/W	0.9989	likely_pathogenic	0.9993	pathogenic	-1.742	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	I
V/Y	0.9949	likely_pathogenic	0.9962	pathogenic	-1.421	Destabilizing	1.0	D	0.827	deleterious	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.