TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23496	70711;70712;70713	chr2:178575646;178575645;178575644	chr2:179440373;179440372;179440371
N2AB	21855	65788;65789;65790	chr2:178575646;178575645;178575644	chr2:179440373;179440372;179440371
N2A	20928	63007;63008;63009	chr2:178575646;178575645;178575644	chr2:179440373;179440372;179440371
N2B	14431	43516;43517;43518	chr2:178575646;178575645;178575644	chr2:179440373;179440372;179440371
Novex-1	14556	43891;43892;43893	chr2:178575646;178575645;178575644	chr2:179440373;179440372;179440371
Novex-2	14623	44092;44093;44094	chr2:178575646;178575645;178575644	chr2:179440373;179440372;179440371
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-58
• Domain position: 62
• Structural Position: 93
• Q(SASA): 0.1182
• 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	None	None	0.244	N	0.532	0.126	0.413891365518	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.663	likely_pathogenic	0.6918	pathogenic	-1.815	Destabilizing	0.027	N	0.402	neutral	N	0.490672171	None	None	N
V/C	0.8911	likely_pathogenic	0.918	pathogenic	-1.438	Destabilizing	0.997	D	0.807	deleterious	None	None	None	None	N
V/D	0.9776	likely_pathogenic	0.987	pathogenic	-2.062	Highly Destabilizing	1.0	D	0.841	deleterious	N	0.511245188	None	None	N
V/E	0.9411	likely_pathogenic	0.9615	pathogenic	-1.814	Destabilizing	0.998	D	0.807	deleterious	None	None	None	None	N
V/F	0.4035	ambiguous	0.4911	ambiguous	-1.051	Destabilizing	0.237	N	0.591	neutral	N	0.498986602	None	None	N
V/G	0.8583	likely_pathogenic	0.8873	pathogenic	-2.386	Highly Destabilizing	0.937	D	0.787	deleterious	D	0.546239157	None	None	N
V/H	0.9751	likely_pathogenic	0.9865	pathogenic	-2.144	Highly Destabilizing	0.999	D	0.85	deleterious	None	None	None	None	N
V/I	0.0668	likely_benign	0.067	benign	-0.221	Destabilizing	None	N	0.197	neutral	N	0.439964877	None	None	N
V/K	0.9699	likely_pathogenic	0.9829	pathogenic	-1.463	Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
V/L	0.2099	likely_benign	0.2456	benign	-0.221	Destabilizing	0.244	N	0.532	neutral	N	0.467695027	None	None	N
V/M	0.267	likely_benign	0.3207	benign	-0.353	Destabilizing	0.993	D	0.649	neutral	None	None	None	None	N
V/N	0.9361	likely_pathogenic	0.963	pathogenic	-1.829	Destabilizing	0.997	D	0.849	deleterious	None	None	None	None	N
V/P	0.9689	likely_pathogenic	0.9789	pathogenic	-0.724	Destabilizing	0.997	D	0.84	deleterious	None	None	None	None	N
V/Q	0.9435	likely_pathogenic	0.9669	pathogenic	-1.59	Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	N
V/R	0.9602	likely_pathogenic	0.9772	pathogenic	-1.469	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
V/S	0.8881	likely_pathogenic	0.9204	pathogenic	-2.518	Highly Destabilizing	0.856	D	0.789	deleterious	None	None	None	None	N
V/T	0.7993	likely_pathogenic	0.8397	pathogenic	-2.098	Highly Destabilizing	0.828	D	0.729	prob.delet.	None	None	None	None	N
V/W	0.9709	likely_pathogenic	0.9827	pathogenic	-1.521	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
V/Y	0.8823	likely_pathogenic	0.9241	pathogenic	-1.094	Destabilizing	0.975	D	0.815	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.