TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31867	95824;95825;95826	chr2:178545511;178545510;178545509	chr2:179410238;179410237;179410236
N2AB	30226	90901;90902;90903	chr2:178545511;178545510;178545509	chr2:179410238;179410237;179410236
N2A	29299	88120;88121;88122	chr2:178545511;178545510;178545509	chr2:179410238;179410237;179410236
N2B	22802	68629;68630;68631	chr2:178545511;178545510;178545509	chr2:179410238;179410237;179410236
Novex-1	22927	69004;69005;69006	chr2:178545511;178545510;178545509	chr2:179410238;179410237;179410236
Novex-2	22994	69205;69206;69207	chr2:178545511;178545510;178545509	chr2:179410238;179410237;179410236
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Fn3-120
• Domain position: 61
• Structural Position: 90
• Q(SASA): 0.5778
• 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
R/G	rs778708400	None	1.0	N	0.649	0.498	0.588622743037	gnomAD-4.0.0	3.42136E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49783E-06	0	0
R/S	None	None	1.0	N	0.708	0.31	0.305086939656	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
R/A	0.8348	likely_pathogenic	0.8098	pathogenic	-0.673	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
R/C	0.3538	ambiguous	0.278	benign	-0.725	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
R/D	0.9483	likely_pathogenic	0.9402	pathogenic	0.018	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
R/E	0.7541	likely_pathogenic	0.7309	pathogenic	0.174	Stabilizing	0.999	D	0.659	neutral	None	None	None	None	N
R/F	0.8343	likely_pathogenic	0.7901	pathogenic	-0.332	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
R/G	0.7693	likely_pathogenic	0.7333	pathogenic	-1.006	Destabilizing	1.0	D	0.649	neutral	N	0.491727992	None	None	N
R/H	0.194	likely_benign	0.1533	benign	-1.247	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
R/I	0.6323	likely_pathogenic	0.5905	pathogenic	0.229	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
R/K	0.2363	likely_benign	0.2246	benign	-0.607	Destabilizing	0.997	D	0.557	neutral	N	0.516076002	None	None	N
R/L	0.5986	likely_pathogenic	0.538	ambiguous	0.229	Stabilizing	1.0	D	0.649	neutral	None	None	None	None	N
R/M	0.644	likely_pathogenic	0.6073	pathogenic	-0.314	Destabilizing	1.0	D	0.774	deleterious	N	0.495704465	None	None	N
R/N	0.8685	likely_pathogenic	0.8511	pathogenic	-0.319	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
R/P	0.9852	likely_pathogenic	0.9819	pathogenic	-0.051	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
R/Q	0.2157	likely_benign	0.1844	benign	-0.35	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
R/S	0.8203	likely_pathogenic	0.7913	pathogenic	-1.029	Destabilizing	1.0	D	0.708	prob.delet.	N	0.493214998	None	None	N
R/T	0.57	likely_pathogenic	0.5446	ambiguous	-0.674	Destabilizing	1.0	D	0.7	prob.neutral	N	0.497026094	None	None	N
R/V	0.6746	likely_pathogenic	0.6289	pathogenic	-0.051	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
R/W	0.4079	ambiguous	0.3243	benign	-0.023	Destabilizing	1.0	D	0.786	deleterious	N	0.504351745	None	None	N
R/Y	0.6515	likely_pathogenic	0.5683	pathogenic	0.248	Stabilizing	1.0	D	0.759	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.