TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31543	94852;94853;94854	chr2:178546801;178546800;178546799	chr2:179411528;179411527;179411526
N2AB	29902	89929;89930;89931	chr2:178546801;178546800;178546799	chr2:179411528;179411527;179411526
N2A	28975	87148;87149;87150	chr2:178546801;178546800;178546799	chr2:179411528;179411527;179411526
N2B	22478	67657;67658;67659	chr2:178546801;178546800;178546799	chr2:179411528;179411527;179411526
Novex-1	22603	68032;68033;68034	chr2:178546801;178546800;178546799	chr2:179411528;179411527;179411526
Novex-2	22670	68233;68234;68235	chr2:178546801;178546800;178546799	chr2:179411528;179411527;179411526
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-118
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.063
• 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
I/M	rs397517759	-1.891	0.627	N	0.565	0.299	0.545825192673	gnomAD-2.1.1	7.67E-05	None	None	None	None	N	None	0	0	None	0	0	None	5.88466E-04	None	0	8.94E-06	0
I/M	rs397517759	-1.891	0.627	N	0.565	0.299	0.545825192673	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07211E-04	0
I/M	rs397517759	-1.891	0.627	N	0.565	0.299	0.545825192673	gnomAD-4.0.0	5.32967E-05	None	None	None	None	N	None	0	0	None	3.37975E-05	0	None	0	1.65071E-04	1.69548E-05	6.80825E-04	3.20184E-05
I/T	rs749659528	-3.616	0.324	D	0.595	0.474	0.719986826817	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/T	rs749659528	-3.616	0.324	D	0.595	0.474	0.719986826817	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
I/T	rs749659528	-3.616	0.324	D	0.595	0.474	0.719986826817	gnomAD-4.0.0	6.81771E-06	None	None	None	None	N	None	0	3.33467E-05	None	0	0	None	0	0	5.08638E-06	3.29446E-05	0
I/V	rs771491701	-2.142	None	N	0.155	0.082	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
I/V	rs771491701	-2.142	None	N	0.155	0.082	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
I/V	rs771491701	-2.142	None	N	0.155	0.082	None	gnomAD-4.0.0	1.30154E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.61072E-05	2.19597E-05	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
I/A	0.9226	likely_pathogenic	0.9092	pathogenic	-3.188	Highly Destabilizing	0.116	N	0.6	neutral	None	None	None	None	N
I/C	0.9796	likely_pathogenic	0.9765	pathogenic	-2.227	Highly Destabilizing	0.944	D	0.775	deleterious	None	None	None	None	N
I/D	0.9997	likely_pathogenic	0.9996	pathogenic	-3.859	Highly Destabilizing	0.818	D	0.821	deleterious	None	None	None	None	N
I/E	0.9987	likely_pathogenic	0.9982	pathogenic	-3.54	Highly Destabilizing	0.818	D	0.802	deleterious	None	None	None	None	N
I/F	0.9559	likely_pathogenic	0.9327	pathogenic	-1.952	Destabilizing	0.69	D	0.589	neutral	None	None	None	None	N
I/G	0.997	likely_pathogenic	0.9962	pathogenic	-3.774	Highly Destabilizing	0.563	D	0.772	deleterious	None	None	None	None	N
I/H	0.9993	likely_pathogenic	0.9991	pathogenic	-3.343	Highly Destabilizing	0.981	D	0.866	deleterious	None	None	None	None	N
I/K	0.9982	likely_pathogenic	0.9974	pathogenic	-2.581	Highly Destabilizing	0.773	D	0.803	deleterious	D	0.542470629	None	None	N
I/L	0.4917	ambiguous	0.4258	ambiguous	-1.402	Destabilizing	0.018	N	0.281	neutral	N	0.505997868	None	None	N
I/M	0.7034	likely_pathogenic	0.6414	pathogenic	-1.495	Destabilizing	0.627	D	0.565	neutral	N	0.499830111	None	None	N
I/N	0.9971	likely_pathogenic	0.996	pathogenic	-3.307	Highly Destabilizing	0.932	D	0.855	deleterious	None	None	None	None	N
I/P	0.9937	likely_pathogenic	0.9918	pathogenic	-1.993	Destabilizing	0.932	D	0.845	deleterious	None	None	None	None	N
I/Q	0.9983	likely_pathogenic	0.9976	pathogenic	-2.968	Highly Destabilizing	0.932	D	0.86	deleterious	None	None	None	None	N
I/R	0.9964	likely_pathogenic	0.9951	pathogenic	-2.524	Highly Destabilizing	0.773	D	0.855	deleterious	D	0.542470629	None	None	N
I/S	0.9852	likely_pathogenic	0.982	pathogenic	-3.821	Highly Destabilizing	0.388	N	0.729	prob.delet.	None	None	None	None	N
I/T	0.8613	likely_pathogenic	0.8359	pathogenic	-3.349	Highly Destabilizing	0.324	N	0.595	neutral	D	0.54221714	None	None	N
I/V	0.0695	likely_benign	0.0703	benign	-1.993	Destabilizing	None	N	0.155	neutral	N	0.39480023	None	None	N
I/W	0.9993	likely_pathogenic	0.999	pathogenic	-2.318	Highly Destabilizing	0.981	D	0.839	deleterious	None	None	None	None	N
I/Y	0.9979	likely_pathogenic	0.9968	pathogenic	-2.197	Highly Destabilizing	0.818	D	0.732	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.