TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32444	97555;97556;97557	chr2:178542426;178542425;178542424	chr2:179407153;179407152;179407151
N2AB	30803	92632;92633;92634	chr2:178542426;178542425;178542424	chr2:179407153;179407152;179407151
N2A	29876	89851;89852;89853	chr2:178542426;178542425;178542424	chr2:179407153;179407152;179407151
N2B	23379	70360;70361;70362	chr2:178542426;178542425;178542424	chr2:179407153;179407152;179407151
Novex-1	23504	70735;70736;70737	chr2:178542426;178542425;178542424	chr2:179407153;179407152;179407151
Novex-2	23571	70936;70937;70938	chr2:178542426;178542425;178542424	chr2:179407153;179407152;179407151
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: Fn3-124
• Domain position: 46
• Structural Position: 60
• Q(SASA): 0.4428
• 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	rs776164829	0.107	1.0	N	0.722	0.446	0.661710244528	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
R/C	rs776164829	0.107	1.0	N	0.722	0.446	0.661710244528	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	4.41E-05	2.06954E-04	0
R/C	rs776164829	0.107	1.0	N	0.722	0.446	0.661710244528	gnomAD-4.0.0	2.16912E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	1.64528E-04	2.79725E-05	1.09782E-05	0
R/H	rs184922462	-1.123	1.0	N	0.67	0.31	0.285698343383	gnomAD-2.1.1	2.42E-05	None	None	None	None	N	None	0	1.16077E-04	None	0	0	None	0	None	0	1.78E-05	0
R/H	rs184922462	-1.123	1.0	N	0.67	0.31	0.285698343383	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	2.94E-05	0	9.56023E-04
R/H	rs184922462	-1.123	1.0	N	0.67	0.31	0.285698343383	gnomAD-4.0.0	4.09039E-05	None	None	None	None	N	None	0	1.00023E-04	None	0	0	None	0	0	4.74692E-05	0	6.40471E-05
R/P	rs184922462	0.447	1.0	N	0.592	0.428	None	gnomAD-2.1.1	2.71667E-04	None	None	None	None	N	None	0	1.16121E-03	None	0	0	None	0	None	0	2.26974E-04	8.43882E-04
R/P	rs184922462	0.447	1.0	N	0.592	0.428	None	gnomAD-3.1.2	2.89249E-04	None	None	None	None	N	None	4.83E-05	1.76817E-03	0	0	0	None	0	0	1.76465E-04	0	1.43403E-03
R/P	rs184922462	0.447	1.0	N	0.592	0.428	None	1000 genomes	3.99361E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	1E-03	None	None	None	0	None
R/P	rs184922462	0.447	1.0	N	0.592	0.428	None	gnomAD-4.0.0	2.41067E-04	None	None	None	None	N	None	7.99723E-05	1.49985E-03	None	0	0	None	0	0	2.28023E-04	0	3.84148E-04

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	0.8234	likely_pathogenic	0.782	pathogenic	-0.029	Destabilizing	0.999	D	0.458	neutral	None	None	None	None	N
R/C	0.3872	ambiguous	0.3171	benign	-0.094	Destabilizing	1.0	D	0.722	prob.delet.	N	0.48233347	None	None	N
R/D	0.9517	likely_pathogenic	0.9393	pathogenic	-0.02	Destabilizing	1.0	D	0.585	neutral	None	None	None	None	N
R/E	0.7939	likely_pathogenic	0.7499	pathogenic	0.057	Stabilizing	0.999	D	0.531	neutral	None	None	None	None	N
R/F	0.8508	likely_pathogenic	0.8118	pathogenic	-0.171	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
R/G	0.7339	likely_pathogenic	0.6665	pathogenic	-0.252	Destabilizing	1.0	D	0.507	neutral	N	0.442652892	None	None	N
R/H	0.2078	likely_benign	0.168	benign	-0.779	Destabilizing	1.0	D	0.67	neutral	N	0.477229612	None	None	N
R/I	0.6152	likely_pathogenic	0.5753	pathogenic	0.53	Stabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
R/K	0.2394	likely_benign	0.2178	benign	-0.084	Destabilizing	0.998	D	0.427	neutral	None	None	None	None	N
R/L	0.5181	ambiguous	0.4698	ambiguous	0.53	Stabilizing	1.0	D	0.507	neutral	N	0.516729363	None	None	N
R/M	0.6596	likely_pathogenic	0.6008	pathogenic	0.088	Stabilizing	1.0	D	0.632	neutral	None	None	None	None	N
R/N	0.8822	likely_pathogenic	0.8547	pathogenic	0.203	Stabilizing	1.0	D	0.629	neutral	None	None	None	None	N
R/P	0.9761	likely_pathogenic	0.9662	pathogenic	0.365	Stabilizing	1.0	D	0.592	neutral	N	0.510072749	None	None	N
R/Q	0.2018	likely_benign	0.1709	benign	0.105	Stabilizing	1.0	D	0.627	neutral	None	None	None	None	N
R/S	0.8495	likely_pathogenic	0.8075	pathogenic	-0.182	Destabilizing	1.0	D	0.551	neutral	N	0.373601025	None	None	N
R/T	0.6989	likely_pathogenic	0.6421	pathogenic	0.039	Stabilizing	1.0	D	0.552	neutral	None	None	None	None	N
R/V	0.7022	likely_pathogenic	0.6605	pathogenic	0.365	Stabilizing	1.0	D	0.651	neutral	None	None	None	None	N
R/W	0.4728	ambiguous	0.3971	ambiguous	-0.18	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
R/Y	0.7171	likely_pathogenic	0.6555	pathogenic	0.216	Stabilizing	1.0	D	0.637	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.