TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32474	97645;97646;97647	chr2:178542336;178542335;178542334	chr2:179407063;179407062;179407061
N2AB	30833	92722;92723;92724	chr2:178542336;178542335;178542334	chr2:179407063;179407062;179407061
N2A	29906	89941;89942;89943	chr2:178542336;178542335;178542334	chr2:179407063;179407062;179407061
N2B	23409	70450;70451;70452	chr2:178542336;178542335;178542334	chr2:179407063;179407062;179407061
Novex-1	23534	70825;70826;70827	chr2:178542336;178542335;178542334	chr2:179407063;179407062;179407061
Novex-2	23601	71026;71027;71028	chr2:178542336;178542335;178542334	chr2:179407063;179407062;179407061
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: Fn3-124
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0722
• 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/M	rs763649965	-1.457	0.942	D	0.626	0.678	0.710806825143	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
V/M	rs763649965	-1.457	0.942	D	0.626	0.678	0.710806825143	gnomAD-4.0.0	1.59234E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85964E-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	0.6536	likely_pathogenic	0.5361	ambiguous	-2.551	Highly Destabilizing	0.058	N	0.321	neutral	D	0.535856443	None	None	N
V/C	0.9495	likely_pathogenic	0.9274	pathogenic	-1.721	Destabilizing	0.998	D	0.753	deleterious	None	None	None	None	N
V/D	0.9987	likely_pathogenic	0.9982	pathogenic	-3.227	Highly Destabilizing	0.993	D	0.878	deleterious	None	None	None	None	N
V/E	0.9957	likely_pathogenic	0.9941	pathogenic	-2.933	Highly Destabilizing	0.971	D	0.841	deleterious	D	0.645967356	None	None	N
V/F	0.9511	likely_pathogenic	0.9108	pathogenic	-1.44	Destabilizing	0.956	D	0.734	prob.delet.	None	None	None	None	N
V/G	0.9189	likely_pathogenic	0.8768	pathogenic	-3.074	Highly Destabilizing	0.942	D	0.851	deleterious	D	0.645967356	None	None	N
V/H	0.999	likely_pathogenic	0.9985	pathogenic	-2.765	Highly Destabilizing	0.998	D	0.879	deleterious	None	None	None	None	N
V/I	0.1234	likely_benign	0.1098	benign	-0.992	Destabilizing	0.019	N	0.226	neutral	None	None	None	None	N
V/K	0.9977	likely_pathogenic	0.997	pathogenic	-2.003	Highly Destabilizing	0.978	D	0.845	deleterious	None	None	None	None	N
V/L	0.8082	likely_pathogenic	0.7328	pathogenic	-0.992	Destabilizing	0.247	N	0.602	neutral	D	0.552373628	None	None	N
V/M	0.8317	likely_pathogenic	0.7178	pathogenic	-1.294	Destabilizing	0.942	D	0.626	neutral	D	0.550099585	None	None	N
V/N	0.9948	likely_pathogenic	0.9926	pathogenic	-2.699	Highly Destabilizing	0.993	D	0.907	deleterious	None	None	None	None	N
V/P	0.9934	likely_pathogenic	0.9948	pathogenic	-1.502	Destabilizing	0.993	D	0.865	deleterious	None	None	None	None	N
V/Q	0.996	likely_pathogenic	0.9941	pathogenic	-2.35	Highly Destabilizing	0.993	D	0.895	deleterious	None	None	None	None	N
V/R	0.9947	likely_pathogenic	0.9929	pathogenic	-2.115	Highly Destabilizing	0.978	D	0.903	deleterious	None	None	None	None	N
V/S	0.9464	likely_pathogenic	0.9113	pathogenic	-3.079	Highly Destabilizing	0.915	D	0.838	deleterious	None	None	None	None	N
V/T	0.8072	likely_pathogenic	0.705	pathogenic	-2.648	Highly Destabilizing	0.86	D	0.603	neutral	None	None	None	None	N
V/W	0.9994	likely_pathogenic	0.9988	pathogenic	-1.773	Destabilizing	0.998	D	0.865	deleterious	None	None	None	None	N
V/Y	0.9959	likely_pathogenic	0.9928	pathogenic	-1.66	Destabilizing	0.978	D	0.757	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.