TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32548	97867;97868;97869	chr2:178541435;178541434;178541433	chr2:179406162;179406161;179406160
N2AB	30907	92944;92945;92946	chr2:178541435;178541434;178541433	chr2:179406162;179406161;179406160
N2A	29980	90163;90164;90165	chr2:178541435;178541434;178541433	chr2:179406162;179406161;179406160
N2B	23483	70672;70673;70674	chr2:178541435;178541434;178541433	chr2:179406162;179406161;179406160
Novex-1	23608	71047;71048;71049	chr2:178541435;178541434;178541433	chr2:179406162;179406161;179406160
Novex-2	23675	71248;71249;71250	chr2:178541435;178541434;178541433	chr2:179406162;179406161;179406160
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Fn3-125
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.3924
• 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/C	rs377599569	-0.674	1.0	N	0.726	0.4	None	gnomAD-2.1.1	6.79E-05	None	None	None	None	N	None	6.61978E-04	5.67E-05	None	0	0	None	3.28E-05	None	0	0	0
R/C	rs377599569	-0.674	1.0	N	0.726	0.4	None	gnomAD-3.1.2	1.31543E-04	None	None	None	None	N	None	4.58893E-04	0	0	2.88018E-04	0	None	0	0	0	0	0
R/C	rs377599569	-0.674	1.0	N	0.726	0.4	None	gnomAD-4.0.0	3.28534E-05	None	None	None	None	N	None	5.47689E-04	3.33556E-05	None	3.37975E-05	0	None	0	0	5.08654E-06	2.19742E-05	1.602E-05
R/H	rs55676195	-1.493	1.0	N	0.613	0.375	None	gnomAD-2.1.1	6.79E-05	None	None	None	None	N	None	2.89711E-04	2.83E-05	None	9.67E-05	0	None	6.55E-05	None	0	6.25E-05	0
R/H	rs55676195	-1.493	1.0	N	0.613	0.375	None	gnomAD-3.1.2	1.51202E-04	None	None	None	None	N	None	4.34531E-04	6.55E-05	0	0	0	None	0	6.32911E-03	2.94E-05	0	0
R/H	rs55676195	-1.493	1.0	N	0.613	0.375	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
R/H	rs55676195	-1.493	1.0	N	0.613	0.375	None	gnomAD-4.0.0	5.33044E-05	None	None	None	None	N	None	4.13322E-04	3.334E-05	None	3.37998E-05	0	None	0	1.15588E-03	3.22153E-05	2.19746E-05	8.00692E-05
R/L	rs55676195	None	0.992	N	0.639	0.42	0.487348339145	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/L	rs55676195	None	0.992	N	0.639	0.42	0.487348339145	gnomAD-4.0.0	6.57402E-06	None	None	None	None	N	None	2.41406E-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	0.4314	ambiguous	0.4441	ambiguous	-0.916	Destabilizing	0.871	D	0.627	neutral	None	None	None	None	N
R/C	0.2279	likely_benign	0.2407	benign	-0.916	Destabilizing	1.0	D	0.726	prob.delet.	N	0.492715497	None	None	N
R/D	0.862	likely_pathogenic	0.8771	pathogenic	-0.057	Destabilizing	0.991	D	0.627	neutral	None	None	None	None	N
R/E	0.5584	ambiguous	0.5845	pathogenic	0.065	Stabilizing	0.97	D	0.532	neutral	None	None	None	None	N
R/F	0.7196	likely_pathogenic	0.7264	pathogenic	-0.768	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
R/G	0.4758	ambiguous	0.4958	ambiguous	-1.222	Destabilizing	0.984	D	0.619	neutral	N	0.516614719	None	None	N
R/H	0.1792	likely_benign	0.1927	benign	-1.412	Destabilizing	1.0	D	0.613	neutral	N	0.512995624	None	None	N
R/I	0.3688	ambiguous	0.3961	ambiguous	-0.092	Destabilizing	0.996	D	0.733	prob.delet.	None	None	None	None	N
R/K	0.1223	likely_benign	0.1296	benign	-0.929	Destabilizing	0.304	N	0.199	neutral	None	None	None	None	N
R/L	0.3116	likely_benign	0.3179	benign	-0.092	Destabilizing	0.992	D	0.639	neutral	N	0.513017054	None	None	N
R/M	0.3568	ambiguous	0.3877	ambiguous	-0.415	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
R/N	0.7357	likely_pathogenic	0.7742	pathogenic	-0.383	Destabilizing	0.97	D	0.556	neutral	None	None	None	None	N
R/P	0.3519	ambiguous	0.3603	ambiguous	-0.347	Destabilizing	0.998	D	0.718	prob.delet.	N	0.456739697	None	None	N
R/Q	0.1338	likely_benign	0.1442	benign	-0.567	Destabilizing	0.991	D	0.583	neutral	None	None	None	None	N
R/S	0.6386	likely_pathogenic	0.6637	pathogenic	-1.208	Destabilizing	0.709	D	0.377	neutral	N	0.49063884	None	None	N
R/T	0.3094	likely_benign	0.3381	benign	-0.905	Destabilizing	0.942	D	0.641	neutral	None	None	None	None	N
R/V	0.397	ambiguous	0.4153	ambiguous	-0.347	Destabilizing	0.996	D	0.664	neutral	None	None	None	None	N
R/W	0.2874	likely_benign	0.3064	benign	-0.39	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
R/Y	0.572	likely_pathogenic	0.604	pathogenic	-0.105	Destabilizing	0.999	D	0.733	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.