TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20390	61393;61394;61395	chr2:178590557;178590556;178590555	chr2:179455284;179455283;179455282
N2AB	18749	56470;56471;56472	chr2:178590557;178590556;178590555	chr2:179455284;179455283;179455282
N2A	17822	53689;53690;53691	chr2:178590557;178590556;178590555	chr2:179455284;179455283;179455282
N2B	11325	34198;34199;34200	chr2:178590557;178590556;178590555	chr2:179455284;179455283;179455282
Novex-1	11450	34573;34574;34575	chr2:178590557;178590556;178590555	chr2:179455284;179455283;179455282
Novex-2	11517	34774;34775;34776	chr2:178590557;178590556;178590555	chr2:179455284;179455283;179455282
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-36
• Domain position: 20
• Structural Position: 22
• Q(SASA): 0.1215
• 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
L/F	None	None	1.0	N	0.76	0.427	0.583177444714	gnomAD-4.0.0	6.84727E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99886E-07	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
L/A	0.9752	likely_pathogenic	0.9717	pathogenic	-2.548	Highly Destabilizing	0.999	D	0.718	prob.delet.	None	None	None	None	N
L/C	0.9718	likely_pathogenic	0.9664	pathogenic	-1.617	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9997	pathogenic	-3.357	Highly Destabilizing	1.0	D	0.933	deleterious	None	None	None	None	N
L/E	0.9986	likely_pathogenic	0.9984	pathogenic	-3.027	Highly Destabilizing	1.0	D	0.92	deleterious	None	None	None	None	N
L/F	0.7532	likely_pathogenic	0.7032	pathogenic	-1.568	Destabilizing	1.0	D	0.76	deleterious	N	0.509226817	None	None	N
L/G	0.9976	likely_pathogenic	0.9972	pathogenic	-3.149	Highly Destabilizing	1.0	D	0.912	deleterious	None	None	None	None	N
L/H	0.9969	likely_pathogenic	0.9962	pathogenic	-2.982	Highly Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
L/I	0.1388	likely_benign	0.1242	benign	-0.73	Destabilizing	0.999	D	0.561	neutral	None	None	None	None	N
L/K	0.9972	likely_pathogenic	0.9969	pathogenic	-2.0	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/M	0.3655	ambiguous	0.3747	ambiguous	-0.87	Destabilizing	1.0	D	0.739	prob.delet.	N	0.509733796	None	None	N
L/N	0.9988	likely_pathogenic	0.9987	pathogenic	-2.798	Highly Destabilizing	1.0	D	0.935	deleterious	None	None	None	None	N
L/P	0.9988	likely_pathogenic	0.9986	pathogenic	-1.329	Destabilizing	1.0	D	0.936	deleterious	None	None	None	None	N
L/Q	0.9967	likely_pathogenic	0.996	pathogenic	-2.384	Highly Destabilizing	1.0	D	0.926	deleterious	None	None	None	None	N
L/R	0.9953	likely_pathogenic	0.9944	pathogenic	-2.203	Highly Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	N
L/S	0.9983	likely_pathogenic	0.998	pathogenic	-3.259	Highly Destabilizing	1.0	D	0.906	deleterious	D	0.539954825	None	None	N
L/T	0.985	likely_pathogenic	0.9811	pathogenic	-2.759	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
L/V	0.267	likely_benign	0.2241	benign	-1.329	Destabilizing	0.999	D	0.586	neutral	N	0.49648459	None	None	N
L/W	0.9856	likely_pathogenic	0.9804	pathogenic	-1.961	Destabilizing	1.0	D	0.867	deleterious	D	0.539954825	None	None	N
L/Y	0.9863	likely_pathogenic	0.9828	pathogenic	-1.748	Destabilizing	1.0	D	0.841	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.