TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34448	103567;103568;103569	chr2:178533273;178533272;178533271	chr2:179398000;179397999;179397998
N2AB	32807	98644;98645;98646	chr2:178533273;178533272;178533271	chr2:179398000;179397999;179397998
N2A	31880	95863;95864;95865	chr2:178533273;178533272;178533271	chr2:179398000;179397999;179397998
N2B	25383	76372;76373;76374	chr2:178533273;178533272;178533271	chr2:179398000;179397999;179397998
Novex-1	25508	76747;76748;76749	chr2:178533273;178533272;178533271	chr2:179398000;179397999;179397998
Novex-2	25575	76948;76949;76950	chr2:178533273;178533272;178533271	chr2:179398000;179397999;179397998
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-162
• Domain position: 86
• Structural Position: 171
• Q(SASA): 0.5772
• 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
Q/R	None	None	0.98	N	0.627	0.379	0.21279746466	gnomAD-4.0.0	2.73658E-06	None	None	None	None	N	None	2.98704E-05	0	None	0	2.51915E-05	None	0	0	0	0	3.31268E-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
Q/A	0.6306	likely_pathogenic	0.6169	pathogenic	-0.574	Destabilizing	0.993	D	0.667	neutral	None	None	None	None	N
Q/C	0.9758	likely_pathogenic	0.9679	pathogenic	0.053	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
Q/D	0.9643	likely_pathogenic	0.9446	pathogenic	0.025	Stabilizing	0.993	D	0.612	neutral	None	None	None	None	N
Q/E	0.2983	likely_benign	0.294	benign	0.065	Stabilizing	0.953	D	0.519	neutral	N	0.410343764	None	None	N
Q/F	0.9659	likely_pathogenic	0.9474	pathogenic	-0.431	Destabilizing	0.998	D	0.803	deleterious	None	None	None	None	N
Q/G	0.8911	likely_pathogenic	0.8716	pathogenic	-0.861	Destabilizing	0.993	D	0.715	prob.delet.	None	None	None	None	N
Q/H	0.8164	likely_pathogenic	0.746	pathogenic	-0.619	Destabilizing	0.265	N	0.343	neutral	N	0.468720064	None	None	N
Q/I	0.8188	likely_pathogenic	0.7924	pathogenic	0.126	Stabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
Q/K	0.5333	ambiguous	0.512	ambiguous	-0.138	Destabilizing	0.99	D	0.604	neutral	N	0.443242829	None	None	N
Q/L	0.6436	likely_pathogenic	0.6089	pathogenic	0.126	Stabilizing	0.99	D	0.721	prob.delet.	N	0.501043126	None	None	N
Q/M	0.7098	likely_pathogenic	0.6893	pathogenic	0.438	Stabilizing	0.999	D	0.662	neutral	None	None	None	None	N
Q/N	0.8512	likely_pathogenic	0.8013	pathogenic	-0.542	Destabilizing	0.985	D	0.624	neutral	None	None	None	None	N
Q/P	0.9645	likely_pathogenic	0.9395	pathogenic	-0.077	Destabilizing	0.999	D	0.745	deleterious	N	0.490615489	None	None	N
Q/R	0.56	ambiguous	0.5192	ambiguous	-0.012	Destabilizing	0.98	D	0.627	neutral	N	0.447112641	None	None	N
Q/S	0.6284	likely_pathogenic	0.598	pathogenic	-0.641	Destabilizing	0.993	D	0.594	neutral	None	None	None	None	N
Q/T	0.5805	likely_pathogenic	0.5506	ambiguous	-0.413	Destabilizing	0.998	D	0.708	prob.delet.	None	None	None	None	N
Q/V	0.6929	likely_pathogenic	0.669	pathogenic	-0.077	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
Q/W	0.9768	likely_pathogenic	0.96	pathogenic	-0.289	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
Q/Y	0.9565	likely_pathogenic	0.9268	pathogenic	-0.092	Destabilizing	0.996	D	0.741	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.