TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14616	44071;44072;44073	chr2:178631202;178631201;178631200	chr2:179495929;179495928;179495927
N2AB	12975	39148;39149;39150	chr2:178631202;178631201;178631200	chr2:179495929;179495928;179495927
N2A	12048	36367;36368;36369	chr2:178631202;178631201;178631200	chr2:179495929;179495928;179495927
N2B	5551	16876;16877;16878	chr2:178631202;178631201;178631200	chr2:179495929;179495928;179495927
Novex-1	5676	17251;17252;17253	chr2:178631202;178631201;178631200	chr2:179495929;179495928;179495927
Novex-2	5743	17452;17453;17454	chr2:178631202;178631201;178631200	chr2:179495929;179495928;179495927
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-97
• Domain position: 31
• Structural Position: 46
• Q(SASA): 0.2259
• 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/A	None	None	0.999	D	0.61	0.794	0.780250927539	gnomAD-4.0.0	6.16008E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29729E-06	0	3.31576E-05

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	0.4967	ambiguous	0.595	pathogenic	-1.854	Destabilizing	0.999	D	0.61	neutral	D	0.685183746	None	None	N
V/C	0.9151	likely_pathogenic	0.9414	pathogenic	-1.047	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
V/D	0.9586	likely_pathogenic	0.9826	pathogenic	-2.247	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
V/E	0.8955	likely_pathogenic	0.9499	pathogenic	-2.119	Highly Destabilizing	1.0	D	0.841	deleterious	D	0.821604042	None	None	N
V/F	0.6038	likely_pathogenic	0.7266	pathogenic	-1.276	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
V/G	0.6251	likely_pathogenic	0.7492	pathogenic	-2.283	Highly Destabilizing	1.0	D	0.842	deleterious	D	0.708100418	None	None	N
V/H	0.9821	likely_pathogenic	0.9915	pathogenic	-1.92	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
V/I	0.1349	likely_benign	0.1447	benign	-0.701	Destabilizing	0.998	D	0.59	neutral	None	None	None	None	N
V/K	0.9555	likely_pathogenic	0.9785	pathogenic	-1.601	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
V/L	0.5436	ambiguous	0.6539	pathogenic	-0.701	Destabilizing	0.997	D	0.642	neutral	D	0.638315239	None	None	N
V/M	0.4684	ambiguous	0.5844	pathogenic	-0.437	Destabilizing	1.0	D	0.757	deleterious	D	0.729914968	None	None	N
V/N	0.9335	likely_pathogenic	0.9672	pathogenic	-1.64	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/P	0.9382	likely_pathogenic	0.9645	pathogenic	-1.056	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
V/Q	0.9157	likely_pathogenic	0.9597	pathogenic	-1.651	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
V/R	0.9278	likely_pathogenic	0.9643	pathogenic	-1.215	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
V/S	0.7247	likely_pathogenic	0.8175	pathogenic	-2.155	Highly Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
V/T	0.605	likely_pathogenic	0.6871	pathogenic	-1.905	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
V/W	0.9893	likely_pathogenic	0.9952	pathogenic	-1.691	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
V/Y	0.9581	likely_pathogenic	0.9793	pathogenic	-1.322	Destabilizing	1.0	D	0.79	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.