TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6236	18931;18932;18933	chr2:178729450;178729449;178729448	chr2:179594177;179594176;179594175
N2AB	5919	17980;17981;17982	chr2:178729450;178729449;178729448	chr2:179594177;179594176;179594175
N2A	4992	15199;15200;15201	chr2:178729450;178729449;178729448	chr2:179594177;179594176;179594175
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: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-46
• Domain position: 38
• Structural Position: 52
• Q(SASA): 1.0117
• 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
N/D	rs758455641	0.43	0.642	N	0.333	0.161	0.0954503805726	gnomAD-2.1.1	2.01E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.64E-05	3.56E-05	0
N/D	rs758455641	0.43	0.642	N	0.333	0.161	0.0954503805726	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
N/D	rs758455641	0.43	0.642	N	0.333	0.161	0.0954503805726	gnomAD-4.0.0	1.02511E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.56868E-05	0	1.43631E-05	0	2.84463E-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
N/A	0.2498	likely_benign	0.2823	benign	-0.141	Destabilizing	0.013	N	0.167	neutral	None	None	None	None	N
N/C	0.3994	ambiguous	0.4088	ambiguous	0.297	Stabilizing	0.995	D	0.381	neutral	None	None	None	None	N
N/D	0.1268	likely_benign	0.1338	benign	0.212	Stabilizing	0.642	D	0.333	neutral	N	0.447722277	None	None	N
N/E	0.3387	likely_benign	0.3689	ambiguous	0.174	Stabilizing	0.329	N	0.298	neutral	None	None	None	None	N
N/F	0.5721	likely_pathogenic	0.6087	pathogenic	-0.56	Destabilizing	0.981	D	0.405	neutral	None	None	None	None	N
N/G	0.183	likely_benign	0.1919	benign	-0.296	Destabilizing	0.003	N	0.134	neutral	None	None	None	None	N
N/H	0.1012	likely_benign	0.107	benign	-0.299	Destabilizing	0.975	D	0.339	neutral	N	0.51389134	None	None	N
N/I	0.3833	ambiguous	0.4328	ambiguous	0.172	Stabilizing	0.927	D	0.454	neutral	N	0.483964587	None	None	N
N/K	0.2414	likely_benign	0.2428	benign	0.121	Stabilizing	0.006	N	0.173	neutral	N	0.430888742	None	None	N
N/L	0.3107	likely_benign	0.3432	ambiguous	0.172	Stabilizing	0.704	D	0.431	neutral	None	None	None	None	N
N/M	0.408	ambiguous	0.4368	ambiguous	0.286	Stabilizing	0.981	D	0.374	neutral	None	None	None	None	N
N/P	0.7379	likely_pathogenic	0.8011	pathogenic	0.094	Stabilizing	0.944	D	0.447	neutral	None	None	None	None	N
N/Q	0.2425	likely_benign	0.2635	benign	-0.235	Destabilizing	0.704	D	0.362	neutral	None	None	None	None	N
N/R	0.2633	likely_benign	0.2691	benign	0.159	Stabilizing	0.543	D	0.322	neutral	None	None	None	None	N
N/S	0.082	likely_benign	0.0848	benign	-0.042	Destabilizing	0.065	N	0.146	neutral	N	0.448223709	None	None	N
N/T	0.1797	likely_benign	0.2036	benign	0.053	Stabilizing	0.27	N	0.301	neutral	N	0.513197907	None	None	N
N/V	0.3871	ambiguous	0.4383	ambiguous	0.094	Stabilizing	0.704	D	0.439	neutral	None	None	None	None	N
N/W	0.753	likely_pathogenic	0.776	pathogenic	-0.615	Destabilizing	0.995	D	0.414	neutral	None	None	None	None	N
N/Y	0.2026	likely_benign	0.2107	benign	-0.319	Destabilizing	0.975	D	0.393	neutral	N	0.460998486	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.