TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28668	86227;86228;86229	chr2:178560130;178560129;178560128	chr2:179424857;179424856;179424855
N2AB	27027	81304;81305;81306	chr2:178560130;178560129;178560128	chr2:179424857;179424856;179424855
N2A	26100	78523;78524;78525	chr2:178560130;178560129;178560128	chr2:179424857;179424856;179424855
N2B	19603	59032;59033;59034	chr2:178560130;178560129;178560128	chr2:179424857;179424856;179424855
Novex-1	19728	59407;59408;59409	chr2:178560130;178560129;178560128	chr2:179424857;179424856;179424855
Novex-2	19795	59608;59609;59610	chr2:178560130;178560129;178560128	chr2:179424857;179424856;179424855
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: Fn3-97
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.086
• 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/K	rs374022393	-2.356	0.988	N	0.813	0.515	0.855298891377	gnomAD-2.1.1	3.23E-05	None	None	None	None	N	None	0	2.32099E-04	None	0	0	None	0	None	0	0	0
I/K	rs374022393	-2.356	0.988	N	0.813	0.515	0.855298891377	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/K	rs374022393	-2.356	0.988	N	0.813	0.515	0.855298891377	gnomAD-4.0.0	8.05661E-06	None	None	None	None	N	None	0	1.50045E-04	None	0	0	None	0	0	1.69527E-06	2.19635E-05	0
I/T	rs374022393	-3.205	0.92	N	0.746	0.423	None	gnomAD-2.1.1	4.65E-05	None	None	None	None	N	None	4.96155E-04	0	None	0	0	None	0	None	0	7.85E-06	0
I/T	rs374022393	-3.205	0.92	N	0.746	0.423	None	gnomAD-3.1.2	1.18331E-04	None	None	None	None	N	None	4.34321E-04	0	0	0	0	None	0	0	0	0	0
I/T	rs374022393	-3.205	0.92	N	0.746	0.423	None	gnomAD-4.0.0	3.78041E-05	None	None	None	None	N	None	5.47309E-04	0	None	0	0	None	0	0	1.44098E-05	1.09818E-05	3.20236E-05
I/V	rs72648225	-1.667	0.021	N	0.213	0.085	None	gnomAD-2.1.1	1.07365E-04	None	None	None	None	N	None	1.24028E-04	0	None	0	0	None	3.27E-05	None	8.00897E-04	4.71E-05	0
I/V	rs72648225	-1.667	0.021	N	0.213	0.085	None	gnomAD-3.1.2	1.31482E-04	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	7.53438E-04	0	1.32283E-04	0	0
I/V	rs72648225	-1.667	0.021	N	0.213	0.085	None	gnomAD-4.0.0	6.56927E-05	None	None	None	None	N	None	4.00555E-05	0	None	0	0	None	5.78143E-04	0	5.34011E-05	2.19621E-05	1.60128E-05

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	0.6809	likely_pathogenic	0.5828	pathogenic	-2.766	Highly Destabilizing	0.079	N	0.52	neutral	None	None	None	None	N
I/C	0.8461	likely_pathogenic	0.8221	pathogenic	-2.67	Highly Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
I/D	0.9947	likely_pathogenic	0.9923	pathogenic	-3.138	Highly Destabilizing	0.997	D	0.822	deleterious	None	None	None	None	N
I/E	0.9851	likely_pathogenic	0.9797	pathogenic	-2.849	Highly Destabilizing	0.991	D	0.814	deleterious	None	None	None	None	N
I/F	0.5045	ambiguous	0.4575	ambiguous	-1.699	Destabilizing	0.991	D	0.733	prob.delet.	None	None	None	None	N
I/G	0.9636	likely_pathogenic	0.9434	pathogenic	-3.35	Highly Destabilizing	0.939	D	0.78	deleterious	None	None	None	None	N
I/H	0.9713	likely_pathogenic	0.9629	pathogenic	-2.884	Highly Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
I/K	0.9631	likely_pathogenic	0.9538	pathogenic	-1.994	Destabilizing	0.988	D	0.813	deleterious	N	0.518051908	None	None	N
I/L	0.1863	likely_benign	0.1819	benign	-1.03	Destabilizing	0.509	D	0.495	neutral	N	0.482861931	None	None	N
I/M	0.1529	likely_benign	0.1424	benign	-1.51	Destabilizing	0.988	D	0.66	neutral	N	0.515403998	None	None	N
I/N	0.911	likely_pathogenic	0.8885	pathogenic	-2.563	Highly Destabilizing	0.997	D	0.835	deleterious	None	None	None	None	N
I/P	0.9953	likely_pathogenic	0.9911	pathogenic	-1.597	Destabilizing	0.997	D	0.828	deleterious	None	None	None	None	N
I/Q	0.957	likely_pathogenic	0.9472	pathogenic	-2.302	Highly Destabilizing	0.997	D	0.832	deleterious	None	None	None	None	N
I/R	0.9428	likely_pathogenic	0.927	pathogenic	-1.948	Destabilizing	0.988	D	0.833	deleterious	N	0.518051908	None	None	N
I/S	0.8422	likely_pathogenic	0.782	pathogenic	-3.275	Highly Destabilizing	0.884	D	0.763	deleterious	None	None	None	None	N
I/T	0.7818	likely_pathogenic	0.7077	pathogenic	-2.818	Highly Destabilizing	0.92	D	0.746	deleterious	N	0.491046883	None	None	N
I/V	0.0766	likely_benign	0.066	benign	-1.597	Destabilizing	0.021	N	0.213	neutral	N	0.414698286	None	None	N
I/W	0.9816	likely_pathogenic	0.9791	pathogenic	-1.968	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
I/Y	0.9137	likely_pathogenic	0.8968	pathogenic	-1.782	Destabilizing	0.997	D	0.837	deleterious	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.