TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25824	77695;77696;77697	chr2:178568662;178568661;178568660	chr2:179433389;179433388;179433387
N2AB	24183	72772;72773;72774	chr2:178568662;178568661;178568660	chr2:179433389;179433388;179433387
N2A	23256	69991;69992;69993	chr2:178568662;178568661;178568660	chr2:179433389;179433388;179433387
N2B	16759	50500;50501;50502	chr2:178568662;178568661;178568660	chr2:179433389;179433388;179433387
Novex-1	16884	50875;50876;50877	chr2:178568662;178568661;178568660	chr2:179433389;179433388;179433387
Novex-2	16951	51076;51077;51078	chr2:178568662;178568661;178568660	chr2:179433389;179433388;179433387
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: Ig-136
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.822
• Predicted PPI site: I

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	rs778684474	-0.137	0.999	D	0.524	0.501	0.732132420435	gnomAD-2.1.1	2.02E-05	None	None	None	None	I	None	0	0	None	0	5.59E-05	None	6.54E-05	None	0	1.79E-05	0
R/C	rs778684474	-0.137	0.999	D	0.524	0.501	0.732132420435	gnomAD-4.0.0	2.19E-05	None	None	None	None	I	None	0	0	None	0	5.04566E-05	None	0	0	1.07954E-05	1.85567E-04	3.31433E-05
R/H	rs376051922	-0.542	0.016	N	0.261	0.1	None	gnomAD-2.1.1	2.51E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	5.5E-05	0
R/H	rs376051922	-0.542	0.016	N	0.261	0.1	None	gnomAD-3.1.2	3.95E-05	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	7.36E-05	0	0
R/H	rs376051922	-0.542	0.016	N	0.261	0.1	None	gnomAD-4.0.0	4.40115E-05	None	None	None	None	I	None	1.3359E-05	0	None	0	2.23184E-05	None	0	0	5.68009E-05	1.09823E-05	1.60169E-05
R/L	rs376051922	0.37	0.846	D	0.575	0.325	0.587417723555	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
R/L	rs376051922	0.37	0.846	D	0.575	0.325	0.587417723555	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/L	rs376051922	0.37	0.846	D	0.575	0.325	0.587417723555	gnomAD-4.0.0	1.23976E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.56265E-05	0	8.47775E-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	0.8904	likely_pathogenic	0.8808	pathogenic	0.098	Stabilizing	0.373	N	0.515	neutral	None	None	None	None	I
R/C	0.3048	likely_benign	0.2669	benign	-0.117	Destabilizing	0.999	D	0.524	neutral	D	0.525713182	None	None	I
R/D	0.973	likely_pathogenic	0.9743	pathogenic	-0.146	Destabilizing	0.742	D	0.581	neutral	None	None	None	None	I
R/E	0.8468	likely_pathogenic	0.8395	pathogenic	-0.078	Destabilizing	0.373	N	0.441	neutral	None	None	None	None	I
R/F	0.7867	likely_pathogenic	0.772	pathogenic	-0.114	Destabilizing	0.953	D	0.521	neutral	None	None	None	None	I
R/G	0.8646	likely_pathogenic	0.8521	pathogenic	-0.095	Destabilizing	0.846	D	0.583	neutral	N	0.495999132	None	None	I
R/H	0.1834	likely_benign	0.161	benign	-0.623	Destabilizing	0.016	N	0.261	neutral	N	0.468181346	None	None	I
R/I	0.5107	ambiguous	0.5002	ambiguous	0.57	Stabilizing	0.953	D	0.532	neutral	None	None	None	None	I
R/K	0.1919	likely_benign	0.1807	benign	-0.023	Destabilizing	0.004	N	0.267	neutral	None	None	None	None	I
R/L	0.5462	ambiguous	0.5349	ambiguous	0.57	Stabilizing	0.846	D	0.575	neutral	D	0.52413063	None	None	I
R/M	0.6347	likely_pathogenic	0.609	pathogenic	0.058	Stabilizing	0.984	D	0.53	neutral	None	None	None	None	I
R/N	0.8941	likely_pathogenic	0.8945	pathogenic	0.13	Stabilizing	0.742	D	0.474	neutral	None	None	None	None	I
R/P	0.9889	likely_pathogenic	0.9904	pathogenic	0.433	Stabilizing	0.975	D	0.562	neutral	N	0.507608927	None	None	I
R/Q	0.2219	likely_benign	0.2028	benign	0.077	Stabilizing	0.742	D	0.53	neutral	None	None	None	None	I
R/S	0.8951	likely_pathogenic	0.8836	pathogenic	-0.135	Destabilizing	0.846	D	0.552	neutral	N	0.501368413	None	None	I
R/T	0.7771	likely_pathogenic	0.7628	pathogenic	0.064	Stabilizing	0.742	D	0.59	neutral	None	None	None	None	I
R/V	0.6708	likely_pathogenic	0.6615	pathogenic	0.433	Stabilizing	0.91	D	0.539	neutral	None	None	None	None	I
R/W	0.3923	ambiguous	0.3692	ambiguous	-0.219	Destabilizing	0.996	D	0.545	neutral	None	None	None	None	I
R/Y	0.5564	ambiguous	0.5336	ambiguous	0.196	Stabilizing	0.91	D	0.565	neutral	None	None	None	None	I

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.