TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32513	97762;97763;97764	chr2:178541540;178541539;178541538	chr2:179406267;179406266;179406265
N2AB	30872	92839;92840;92841	chr2:178541540;178541539;178541538	chr2:179406267;179406266;179406265
N2A	29945	90058;90059;90060	chr2:178541540;178541539;178541538	chr2:179406267;179406266;179406265
N2B	23448	70567;70568;70569	chr2:178541540;178541539;178541538	chr2:179406267;179406266;179406265
Novex-1	23573	70942;70943;70944	chr2:178541540;178541539;178541538	chr2:179406267;179406266;179406265
Novex-2	23640	71143;71144;71145	chr2:178541540;178541539;178541538	chr2:179406267;179406266;179406265
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: 15
• Structural Position: 17
• Q(SASA): 0.4224
• 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	rs1279110183	-0.419	1.0	D	0.612	0.434	0.613939331864	gnomAD-2.1.1	1.08E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	2.37E-05	0
R/C	rs1279110183	-0.419	1.0	D	0.612	0.434	0.613939331864	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	2.94E-05	0	0
R/C	rs1279110183	-0.419	1.0	D	0.612	0.434	0.613939331864	gnomAD-4.0.0	8.06392E-06	None	None	None	None	N	None	2.67187E-05	0	None	0	0	None	0	0	8.48178E-06	1.10178E-05	0
R/H	rs201080904	-1.285	0.079	N	0.126	0.178	None	gnomAD-2.1.1	5.04105E-04	None	None	None	None	N	None	0	2.85E-05	None	3.01732E-03	0	None	6.95687E-04	None	4.01E-05	6.38479E-04	7.08015E-04
R/H	rs201080904	-1.285	0.079	N	0.126	0.178	None	gnomAD-3.1.2	4.01026E-04	None	None	None	None	N	None	7.24E-05	3.92927E-04	0	2.59217E-03	0	None	0	3.16456E-03	5.58528E-04	6.21118E-04	4.79386E-04
R/H	rs201080904	-1.285	0.079	N	0.126	0.178	None	gnomAD-4.0.0	5.7929E-04	None	None	None	None	N	None	5.33604E-05	1.33543E-04	None	2.84245E-03	0	None	6.25645E-05	1.32319E-03	6.06425E-04	7.38113E-04	7.0488E-04
R/P	None	None	0.998	N	0.565	0.331	0.367612772649	gnomAD-4.0.0	7.53378E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00079E-06	0	1.65799E-05
R/S	None	None	0.983	N	0.478	0.444	0.316494231283	gnomAD-4.0.0	6.84932E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00105E-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
R/A	0.3925	ambiguous	0.3834	ambiguous	-0.548	Destabilizing	0.969	D	0.48	neutral	None	None	None	None	N
R/C	0.1843	likely_benign	0.1732	benign	-0.431	Destabilizing	1.0	D	0.612	neutral	D	0.523175332	None	None	N
R/D	0.795	likely_pathogenic	0.8006	pathogenic	-0.25	Destabilizing	0.969	D	0.522	neutral	None	None	None	None	N
R/E	0.447	ambiguous	0.4531	ambiguous	-0.184	Destabilizing	0.939	D	0.422	neutral	None	None	None	None	N
R/F	0.7002	likely_pathogenic	0.6859	pathogenic	-0.737	Destabilizing	0.991	D	0.597	neutral	None	None	None	None	N
R/G	0.2623	likely_benign	0.2612	benign	-0.782	Destabilizing	0.983	D	0.526	neutral	N	0.456795625	None	None	N
R/H	0.1115	likely_benign	0.1097	benign	-1.202	Destabilizing	0.079	N	0.126	neutral	N	0.475882818	None	None	N
R/I	0.5379	ambiguous	0.5228	ambiguous	0.052	Stabilizing	0.997	D	0.599	neutral	None	None	None	None	N
R/K	0.1086	likely_benign	0.1053	benign	-0.612	Destabilizing	0.863	D	0.432	neutral	None	None	None	None	N
R/L	0.3836	ambiguous	0.3636	ambiguous	0.052	Stabilizing	0.983	D	0.537	neutral	D	0.522655257	None	None	N
R/M	0.4384	ambiguous	0.4378	ambiguous	-0.069	Destabilizing	0.999	D	0.487	neutral	None	None	None	None	N
R/N	0.653	likely_pathogenic	0.6595	pathogenic	-0.047	Destabilizing	0.939	D	0.427	neutral	None	None	None	None	N
R/P	0.6509	likely_pathogenic	0.6276	pathogenic	-0.128	Destabilizing	0.998	D	0.565	neutral	N	0.465529751	None	None	N
R/Q	0.1164	likely_benign	0.1142	benign	-0.323	Destabilizing	0.969	D	0.495	neutral	None	None	None	None	N
R/S	0.5049	ambiguous	0.5107	ambiguous	-0.651	Destabilizing	0.983	D	0.478	neutral	N	0.423680342	None	None	N
R/T	0.4206	ambiguous	0.4259	ambiguous	-0.441	Destabilizing	0.969	D	0.5	neutral	None	None	None	None	N
R/V	0.5688	likely_pathogenic	0.5517	ambiguous	-0.128	Destabilizing	0.997	D	0.555	neutral	None	None	None	None	N
R/W	0.2563	likely_benign	0.2499	benign	-0.556	Destabilizing	0.999	D	0.662	neutral	None	None	None	None	N
R/Y	0.5021	ambiguous	0.4862	ambiguous	-0.197	Destabilizing	0.982	D	0.518	neutral	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.