TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17678	53257;53258;53259	chr2:178607656;178607655;178607654	chr2:179472383;179472382;179472381
N2AB	16037	48334;48335;48336	chr2:178607656;178607655;178607654	chr2:179472383;179472382;179472381
N2A	15110	45553;45554;45555	chr2:178607656;178607655;178607654	chr2:179472383;179472382;179472381
N2B	8613	26062;26063;26064	chr2:178607656;178607655;178607654	chr2:179472383;179472382;179472381
Novex-1	8738	26437;26438;26439	chr2:178607656;178607655;178607654	chr2:179472383;179472382;179472381
Novex-2	8805	26638;26639;26640	chr2:178607656;178607655;178607654	chr2:179472383;179472382;179472381
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-113
• Domain position: 2
• Structural Position: 3
• Q(SASA): 0.4554
• 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/F	rs1423968417	None	1.0	N	0.747	0.333	0.815354353143	gnomAD-4.0.0	1.59292E-06	None	None	None	None	I	None	0	0	None	0	2.7804E-05	None	0	0	0	0	0
V/L	None	None	0.997	N	0.539	0.335	0.452640719197	gnomAD-4.0.0	1.59292E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.861E-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
V/A	0.5702	likely_pathogenic	0.5686	pathogenic	-0.661	Destabilizing	0.999	D	0.555	neutral	N	0.504520575	None	None	I
V/C	0.8724	likely_pathogenic	0.8734	pathogenic	-0.789	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	I
V/D	0.9414	likely_pathogenic	0.9462	pathogenic	-0.124	Destabilizing	1.0	D	0.774	deleterious	D	0.524589203	None	None	I
V/E	0.8703	likely_pathogenic	0.8733	pathogenic	-0.196	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
V/F	0.4963	ambiguous	0.4959	ambiguous	-0.68	Destabilizing	1.0	D	0.747	deleterious	N	0.465330255	None	None	I
V/G	0.6745	likely_pathogenic	0.6867	pathogenic	-0.846	Destabilizing	1.0	D	0.743	deleterious	D	0.524589203	None	None	I
V/H	0.9651	likely_pathogenic	0.9649	pathogenic	-0.425	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
V/I	0.1204	likely_benign	0.1179	benign	-0.307	Destabilizing	0.997	D	0.506	neutral	N	0.423539561	None	None	I
V/K	0.9239	likely_pathogenic	0.9269	pathogenic	-0.58	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
V/L	0.405	ambiguous	0.4138	ambiguous	-0.307	Destabilizing	0.997	D	0.539	neutral	N	0.43931709	None	None	I
V/M	0.331	likely_benign	0.3272	benign	-0.476	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
V/N	0.8694	likely_pathogenic	0.8811	pathogenic	-0.375	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
V/P	0.9735	likely_pathogenic	0.9753	pathogenic	-0.389	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
V/Q	0.8292	likely_pathogenic	0.8346	pathogenic	-0.532	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
V/R	0.8821	likely_pathogenic	0.8926	pathogenic	-0.165	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
V/S	0.7302	likely_pathogenic	0.7431	pathogenic	-0.808	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
V/T	0.615	likely_pathogenic	0.6196	pathogenic	-0.766	Destabilizing	0.999	D	0.611	neutral	None	None	None	None	I
V/W	0.973	likely_pathogenic	0.9733	pathogenic	-0.785	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	I
V/Y	0.9184	likely_pathogenic	0.9194	pathogenic	-0.487	Destabilizing	1.0	D	0.755	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.