TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22917	68974;68975;68976	chr2:178577677;178577676;178577675	chr2:179442404;179442403;179442402
N2AB	21276	64051;64052;64053	chr2:178577677;178577676;178577675	chr2:179442404;179442403;179442402
N2A	20349	61270;61271;61272	chr2:178577677;178577676;178577675	chr2:179442404;179442403;179442402
N2B	13852	41779;41780;41781	chr2:178577677;178577676;178577675	chr2:179442404;179442403;179442402
Novex-1	13977	42154;42155;42156	chr2:178577677;178577676;178577675	chr2:179442404;179442403;179442402
Novex-2	14044	42355;42356;42357	chr2:178577677;178577676;178577675	chr2:179442404;179442403;179442402
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-54
• Domain position: 77
• Structural Position: 109
• Q(SASA): 0.1941
• 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/K	rs2046750925	None	0.006	N	0.317	0.131	0.143124449307	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
R/K	rs2046750925	None	0.006	N	0.317	0.131	0.143124449307	gnomAD-4.0.0	6.57497E-06	None	None	None	None	N	None	2.41301E-05	0	None	0	0	None	0	0	0	0	0
R/T	None	None	0.822	N	0.621	0.287	0.417586769301	gnomAD-4.0.0	1.59247E-06	None	None	None	None	N	None	5.66187E-05	0	None	0	0	None	0	0	0	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	0.7031	likely_pathogenic	0.7149	pathogenic	-1.547	Destabilizing	0.754	D	0.627	neutral	None	None	None	None	N
R/C	0.2172	likely_benign	0.2146	benign	-1.693	Destabilizing	0.998	D	0.732	prob.delet.	None	None	None	None	N
R/D	0.9599	likely_pathogenic	0.9639	pathogenic	-0.826	Destabilizing	0.956	D	0.681	prob.neutral	None	None	None	None	N
R/E	0.733	likely_pathogenic	0.739	pathogenic	-0.643	Destabilizing	0.754	D	0.648	neutral	None	None	None	None	N
R/F	0.6361	likely_pathogenic	0.6241	pathogenic	-0.977	Destabilizing	0.993	D	0.752	deleterious	None	None	None	None	N
R/G	0.6818	likely_pathogenic	0.695	pathogenic	-1.885	Destabilizing	0.822	D	0.659	neutral	N	0.510517037	None	None	N
R/H	0.187	likely_benign	0.1845	benign	-1.857	Destabilizing	0.978	D	0.653	neutral	None	None	None	None	N
R/I	0.2972	likely_benign	0.291	benign	-0.593	Destabilizing	0.97	D	0.749	deleterious	N	0.432113398	None	None	N
R/K	0.1202	likely_benign	0.1238	benign	-1.49	Destabilizing	0.006	N	0.317	neutral	N	0.499317038	None	None	N
R/L	0.3244	likely_benign	0.3225	benign	-0.593	Destabilizing	0.86	D	0.659	neutral	None	None	None	None	N
R/M	0.3434	ambiguous	0.3194	benign	-1.048	Destabilizing	0.998	D	0.643	neutral	None	None	None	None	N
R/N	0.8808	likely_pathogenic	0.8922	pathogenic	-1.25	Destabilizing	0.956	D	0.637	neutral	None	None	None	None	N
R/P	0.9883	likely_pathogenic	0.9895	pathogenic	-0.896	Destabilizing	0.978	D	0.718	prob.delet.	None	None	None	None	N
R/Q	0.1672	likely_benign	0.163	benign	-1.182	Destabilizing	0.956	D	0.66	neutral	None	None	None	None	N
R/S	0.7766	likely_pathogenic	0.7919	pathogenic	-2.049	Highly Destabilizing	0.822	D	0.613	neutral	N	0.481848785	None	None	N
R/T	0.4038	ambiguous	0.4259	ambiguous	-1.666	Destabilizing	0.822	D	0.621	neutral	N	0.482867505	None	None	N
R/V	0.4428	ambiguous	0.4441	ambiguous	-0.896	Destabilizing	0.956	D	0.725	prob.delet.	None	None	None	None	N
R/W	0.2615	likely_benign	0.241	benign	-0.571	Destabilizing	0.998	D	0.69	prob.neutral	None	None	None	None	N
R/Y	0.5344	ambiguous	0.5285	ambiguous	-0.336	Destabilizing	0.993	D	0.725	prob.delet.	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.