TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4969	15130;15131;15132	chr2:178735541;178735540;178735539	chr2:179600268;179600267;179600266
N2AB	4652	14179;14180;14181	chr2:178735541;178735540;178735539	chr2:179600268;179600267;179600266
N2A	3725	11398;11399;11400	chr2:178735541;178735540;178735539	chr2:179600268;179600267;179600266
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-32
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.1788
• 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
S/G	None	None	0.98	D	0.551	0.307	0.296679040009	gnomAD-4.0.0	1.63519E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.51616E-05	0
S/N	rs762810073	-0.381	0.99	N	0.591	0.302	0.280987212366	gnomAD-2.1.1	8.54E-06	None	None	None	None	N	None	0	0	None	0	5.84E-05	None	0	None	0	9.28E-06	0
S/N	rs762810073	-0.381	0.99	N	0.591	0.302	0.280987212366	gnomAD-4.0.0	1.63777E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.91795E-06	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
S/A	0.0778	likely_benign	0.0839	benign	-0.936	Destabilizing	0.469	N	0.279	neutral	None	None	None	None	N
S/C	0.1144	likely_benign	0.1272	benign	-0.475	Destabilizing	1.0	D	0.677	prob.neutral	D	0.577622495	None	None	N
S/D	0.291	likely_benign	0.3547	ambiguous	0.047	Stabilizing	0.971	D	0.541	neutral	None	None	None	None	N
S/E	0.5038	ambiguous	0.5791	pathogenic	0.016	Stabilizing	0.469	N	0.383	neutral	None	None	None	None	N
S/F	0.1792	likely_benign	0.2128	benign	-1.263	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
S/G	0.1149	likely_benign	0.1303	benign	-1.142	Destabilizing	0.98	D	0.551	neutral	D	0.576684026	None	None	N
S/H	0.3493	ambiguous	0.3991	ambiguous	-1.597	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
S/I	0.1615	likely_benign	0.1987	benign	-0.495	Destabilizing	0.997	D	0.745	deleterious	N	0.499167265	None	None	N
S/K	0.6863	likely_pathogenic	0.7551	pathogenic	-0.612	Destabilizing	0.985	D	0.545	neutral	None	None	None	None	N
S/L	0.1092	likely_benign	0.1297	benign	-0.495	Destabilizing	0.985	D	0.683	prob.neutral	None	None	None	None	N
S/M	0.2528	likely_benign	0.305	benign	-0.074	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
S/N	0.1582	likely_benign	0.188	benign	-0.426	Destabilizing	0.99	D	0.591	neutral	N	0.509023002	None	None	N
S/P	0.8265	likely_pathogenic	0.8738	pathogenic	-0.611	Destabilizing	0.998	D	0.711	prob.delet.	None	None	None	None	N
S/Q	0.528	ambiguous	0.583	pathogenic	-0.643	Destabilizing	0.996	D	0.586	neutral	None	None	None	None	N
S/R	0.557	ambiguous	0.6153	pathogenic	-0.469	Destabilizing	0.994	D	0.713	prob.delet.	N	0.503970995	None	None	N
S/T	0.0922	likely_benign	0.1041	benign	-0.562	Destabilizing	0.98	D	0.559	neutral	N	0.485524716	None	None	N
S/V	0.1604	likely_benign	0.192	benign	-0.611	Destabilizing	0.985	D	0.687	prob.neutral	None	None	None	None	N
S/W	0.3786	ambiguous	0.4143	ambiguous	-1.16	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
S/Y	0.1803	likely_benign	0.2063	benign	-0.929	Destabilizing	0.999	D	0.745	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.