TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33483	100672;100673;100674	chr2:178536300;178536299;178536298	chr2:179401027;179401026;179401025
N2AB	31842	95749;95750;95751	chr2:178536300;178536299;178536298	chr2:179401027;179401026;179401025
N2A	30915	92968;92969;92970	chr2:178536300;178536299;178536298	chr2:179401027;179401026;179401025
N2B	24418	73477;73478;73479	chr2:178536300;178536299;178536298	chr2:179401027;179401026;179401025
Novex-1	24543	73852;73853;73854	chr2:178536300;178536299;178536298	chr2:179401027;179401026;179401025
Novex-2	24610	74053;74054;74055	chr2:178536300;178536299;178536298	chr2:179401027;179401026;179401025
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-131
• Domain position: 92
• Structural Position: 125
• Q(SASA): 0.6877
• 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
E/D	rs762690616	-0.059	0.001	N	0.093	0.092	0.12205267543	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.81E-05	None	0	8.88E-06	0
E/D	rs762690616	-0.059	0.001	N	0.093	0.092	0.12205267543	gnomAD-4.0.0	1.84754E-05	None	None	None	None	N	None	2.98811E-05	0	None	0	0	None	0	0	1.52914E-05	9.27665E-05	1.65695E-05
E/K	rs368321767	None	0.335	N	0.399	0.193	0.218112801441	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs368321767	None	0.335	N	0.399	0.193	0.218112801441	gnomAD-4.0.0	6.57117E-06	None	None	None	None	N	None	2.41301E-05	0	None	0	0	None	0	0	0	0	0
E/Q	rs368321767	0.335	0.013	N	0.235	0.065	None	gnomAD-2.1.1	1.92966E-04	None	None	None	None	N	None	0	5.67E-05	None	0	0	None	9.82E-05	None	4E-05	3.5951E-04	2.81532E-04
E/Q	rs368321767	0.335	0.013	N	0.235	0.065	None	gnomAD-3.1.2	1.7085E-04	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	3.52765E-04	0	4.78011E-04
E/Q	rs368321767	0.335	0.013	N	0.235	0.065	None	gnomAD-4.0.0	3.03677E-04	None	None	None	None	N	None	4.00491E-05	5.00317E-05	None	0	0	None	6.25489E-05	0	3.89064E-04	5.49016E-05	2.56221E-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
E/A	0.1369	likely_benign	0.1214	benign	-0.313	Destabilizing	0.013	N	0.297	neutral	N	0.482806003	None	None	N
E/C	0.8167	likely_pathogenic	0.77	pathogenic	-0.149	Destabilizing	0.991	D	0.475	neutral	None	None	None	None	N
E/D	0.0936	likely_benign	0.0712	benign	-0.287	Destabilizing	0.001	N	0.093	neutral	N	0.417949235	None	None	N
E/F	0.7169	likely_pathogenic	0.6678	pathogenic	-0.168	Destabilizing	0.966	D	0.485	neutral	None	None	None	None	N
E/G	0.1603	likely_benign	0.1479	benign	-0.502	Destabilizing	0.501	D	0.415	neutral	N	0.500103685	None	None	N
E/H	0.4699	ambiguous	0.4118	ambiguous	0.163	Stabilizing	0.905	D	0.316	neutral	None	None	None	None	N
E/I	0.3274	likely_benign	0.2706	benign	0.15	Stabilizing	0.905	D	0.522	neutral	None	None	None	None	N
E/K	0.144	likely_benign	0.1418	benign	0.233	Stabilizing	0.335	N	0.399	neutral	N	0.47191700599999997	None	None	N
E/L	0.3453	ambiguous	0.2841	benign	0.15	Stabilizing	0.571	D	0.471	neutral	None	None	None	None	N
E/M	0.4608	ambiguous	0.3953	ambiguous	0.134	Stabilizing	0.973	D	0.437	neutral	None	None	None	None	N
E/N	0.2042	likely_benign	0.1612	benign	-0.057	Destabilizing	0.4	N	0.378	neutral	None	None	None	None	N
E/P	0.3647	ambiguous	0.3396	benign	0.016	Stabilizing	0.905	D	0.401	neutral	None	None	None	None	N
E/Q	0.1522	likely_benign	0.1338	benign	-0.013	Destabilizing	0.013	N	0.235	neutral	N	0.484499514	None	None	N
E/R	0.2713	likely_benign	0.2776	benign	0.495	Stabilizing	0.4	N	0.371	neutral	None	None	None	None	N
E/S	0.1627	likely_benign	0.1378	benign	-0.23	Destabilizing	0.216	N	0.327	neutral	None	None	None	None	N
E/T	0.204	likely_benign	0.1675	benign	-0.074	Destabilizing	0.571	D	0.32	neutral	None	None	None	None	N
E/V	0.2055	likely_benign	0.1755	benign	0.016	Stabilizing	0.501	D	0.43	neutral	N	0.471511574	None	None	N
E/W	0.9039	likely_pathogenic	0.8849	pathogenic	-0.03	Destabilizing	0.991	D	0.557	neutral	None	None	None	None	N
E/Y	0.5847	likely_pathogenic	0.5314	ambiguous	0.066	Stabilizing	0.966	D	0.471	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.