TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22391	67396;67397;67398	chr2:178580116;178580115;178580114	chr2:179444843;179444842;179444841
N2AB	20750	62473;62474;62475	chr2:178580116;178580115;178580114	chr2:179444843;179444842;179444841
N2A	19823	59692;59693;59694	chr2:178580116;178580115;178580114	chr2:179444843;179444842;179444841
N2B	13326	40201;40202;40203	chr2:178580116;178580115;178580114	chr2:179444843;179444842;179444841
Novex-1	13451	40576;40577;40578	chr2:178580116;178580115;178580114	chr2:179444843;179444842;179444841
Novex-2	13518	40777;40778;40779	chr2:178580116;178580115;178580114	chr2:179444843;179444842;179444841
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: Fn3-50
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0746
• 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	rs756952687	-0.501	0.618	N	0.571	0.265	0.566084962815	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	1.65893E-04
V/L	rs756952687	-0.501	0.618	N	0.571	0.265	0.566084962815	gnomAD-4.0.0	6.36878E-06	None	None	None	None	N	None	0	4.57436E-05	None	0	0	None	0	0	2.86031E-06	0	3.02645E-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	0.9299	likely_pathogenic	0.9231	pathogenic	-2.508	Highly Destabilizing	0.958	D	0.625	neutral	D	0.555631495	None	None	N
V/C	0.9811	likely_pathogenic	0.9719	pathogenic	-1.852	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
V/D	0.9987	likely_pathogenic	0.9985	pathogenic	-3.346	Highly Destabilizing	0.998	D	0.879	deleterious	None	None	None	None	N
V/E	0.9943	likely_pathogenic	0.994	pathogenic	-3.014	Highly Destabilizing	0.998	D	0.87	deleterious	D	0.567748269	None	None	N
V/F	0.8743	likely_pathogenic	0.8255	pathogenic	-1.325	Destabilizing	0.991	D	0.833	deleterious	None	None	None	None	N
V/G	0.9612	likely_pathogenic	0.9629	pathogenic	-3.125	Highly Destabilizing	0.994	D	0.877	deleterious	D	0.567748269	None	None	N
V/H	0.9986	likely_pathogenic	0.9981	pathogenic	-2.97	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
V/I	0.084	likely_benign	0.0683	benign	-0.694	Destabilizing	0.067	N	0.322	neutral	N	0.464497962	None	None	N
V/K	0.9955	likely_pathogenic	0.9945	pathogenic	-1.91	Destabilizing	0.995	D	0.871	deleterious	None	None	None	None	N
V/L	0.5019	ambiguous	0.3806	ambiguous	-0.694	Destabilizing	0.618	D	0.571	neutral	N	0.4883849	None	None	N
V/M	0.806	likely_pathogenic	0.7089	pathogenic	-1.026	Destabilizing	0.991	D	0.75	deleterious	None	None	None	None	N
V/N	0.9961	likely_pathogenic	0.9948	pathogenic	-2.62	Highly Destabilizing	0.998	D	0.889	deleterious	None	None	None	None	N
V/P	0.9931	likely_pathogenic	0.9927	pathogenic	-1.282	Destabilizing	0.998	D	0.876	deleterious	None	None	None	None	N
V/Q	0.9945	likely_pathogenic	0.993	pathogenic	-2.224	Highly Destabilizing	0.998	D	0.899	deleterious	None	None	None	None	N
V/R	0.9907	likely_pathogenic	0.9888	pathogenic	-2.06	Highly Destabilizing	0.998	D	0.895	deleterious	None	None	None	None	N
V/S	0.9858	likely_pathogenic	0.9837	pathogenic	-3.123	Highly Destabilizing	0.995	D	0.875	deleterious	None	None	None	None	N
V/T	0.9487	likely_pathogenic	0.9401	pathogenic	-2.63	Highly Destabilizing	0.968	D	0.71	prob.delet.	None	None	None	None	N
V/W	0.9987	likely_pathogenic	0.9976	pathogenic	-1.858	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
V/Y	0.9927	likely_pathogenic	0.9888	pathogenic	-1.6	Destabilizing	0.995	D	0.833	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.