TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27245	81958;81959;81960	chr2:178564399;178564398;178564397	chr2:179429126;179429125;179429124
N2AB	25604	77035;77036;77037	chr2:178564399;178564398;178564397	chr2:179429126;179429125;179429124
N2A	24677	74254;74255;74256	chr2:178564399;178564398;178564397	chr2:179429126;179429125;179429124
N2B	18180	54763;54764;54765	chr2:178564399;178564398;178564397	chr2:179429126;179429125;179429124
Novex-1	18305	55138;55139;55140	chr2:178564399;178564398;178564397	chr2:179429126;179429125;179429124
Novex-2	18372	55339;55340;55341	chr2:178564399;178564398;178564397	chr2:179429126;179429125;179429124
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-86
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0931
• 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/L	rs777316227	-0.81	0.997	N	0.696	0.507	0.7647777765	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
V/L	rs777316227	-0.81	0.997	N	0.696	0.507	0.7647777765	gnomAD-4.0.0	1.02648E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.34925E-05	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
V/A	0.8374	likely_pathogenic	0.8138	pathogenic	-2.62	Highly Destabilizing	0.999	D	0.673	neutral	D	0.557581549	None	None	N
V/C	0.9578	likely_pathogenic	0.956	pathogenic	-2.021	Highly Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
V/D	0.999	likely_pathogenic	0.9988	pathogenic	-3.336	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
V/E	0.9966	likely_pathogenic	0.9961	pathogenic	-3.036	Highly Destabilizing	1.0	D	0.885	deleterious	D	0.652700131	None	None	N
V/F	0.9698	likely_pathogenic	0.9463	pathogenic	-1.297	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
V/G	0.9609	likely_pathogenic	0.9544	pathogenic	-3.172	Highly Destabilizing	1.0	D	0.893	deleterious	D	0.652700131	None	None	N
V/H	0.9994	likely_pathogenic	0.9991	pathogenic	-2.878	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
V/I	0.1145	likely_benign	0.0916	benign	-0.997	Destabilizing	0.997	D	0.648	neutral	N	0.520191821	None	None	N
V/K	0.9984	likely_pathogenic	0.9981	pathogenic	-1.954	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
V/L	0.841	likely_pathogenic	0.7558	pathogenic	-0.997	Destabilizing	0.997	D	0.696	prob.neutral	N	0.521102642	None	None	N
V/M	0.8855	likely_pathogenic	0.8189	pathogenic	-1.387	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
V/N	0.9944	likely_pathogenic	0.9931	pathogenic	-2.569	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
V/P	0.9976	likely_pathogenic	0.9973	pathogenic	-1.524	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
V/Q	0.9968	likely_pathogenic	0.9961	pathogenic	-2.223	Highly Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
V/R	0.9962	likely_pathogenic	0.9957	pathogenic	-2.001	Highly Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
V/S	0.9663	likely_pathogenic	0.9598	pathogenic	-3.048	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
V/T	0.9326	likely_pathogenic	0.9239	pathogenic	-2.61	Highly Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
V/W	0.9996	likely_pathogenic	0.9993	pathogenic	-1.789	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
V/Y	0.9973	likely_pathogenic	0.9962	pathogenic	-1.611	Destabilizing	1.0	D	0.829	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.