TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5536	16831;16832;16833	chr2:178732455;178732454;178732453	chr2:179597182;179597181;179597180
N2AB	5219	15880;15881;15882	chr2:178732455;178732454;178732453	chr2:179597182;179597181;179597180
N2A	4292	13099;13100;13101	chr2:178732455;178732454;178732453	chr2:179597182;179597181;179597180
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-38
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.4875
• 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/K	rs1386348152	0.491	None	N	0.161	0.121	0.168933306366	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	0	None	0	5.61E-05	None	0	None	0	0	0
N/K	rs1386348152	0.491	None	N	0.161	0.121	0.168933306366	gnomAD-4.0.0	1.60937E-06	None	None	None	None	N	None	0	0	None	0	2.78458E-05	None	0	0	0	0	0
N/S	rs1380672169	-0.175	0.012	N	0.347	0.099	0.193865811164	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	2.95E-05	None	0	0	None	0	None	0	0	0
N/S	rs1380672169	-0.175	0.012	N	0.347	0.099	0.193865811164	gnomAD-4.0.0	1.6095E-06	None	None	None	None	N	None	0	2.32288E-05	None	0	0	None	0	0	0	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
N/A	0.1318	likely_benign	0.1557	benign	-0.708	Destabilizing	None	N	0.289	neutral	None	None	None	None	N
N/C	0.2664	likely_benign	0.2928	benign	0.175	Stabilizing	0.864	D	0.522	neutral	None	None	None	None	N
N/D	0.0807	likely_benign	0.1046	benign	-0.254	Destabilizing	None	N	0.155	neutral	N	0.461716734	None	None	N
N/E	0.1947	likely_benign	0.242	benign	-0.272	Destabilizing	0.016	N	0.381	neutral	None	None	None	None	N
N/F	0.3195	likely_benign	0.3715	ambiguous	-1.043	Destabilizing	0.214	N	0.561	neutral	None	None	None	None	N
N/G	0.2243	likely_benign	0.2626	benign	-0.897	Destabilizing	0.016	N	0.35	neutral	None	None	None	None	N
N/H	0.0792	likely_benign	0.0829	benign	-0.944	Destabilizing	0.295	N	0.529	neutral	N	0.394627737	None	None	N
N/I	0.1368	likely_benign	0.153	benign	-0.283	Destabilizing	0.029	N	0.517	neutral	N	0.470048216	None	None	N
N/K	0.1585	likely_benign	0.1854	benign	0.062	Stabilizing	None	N	0.161	neutral	N	0.435548853	None	None	N
N/L	0.1533	likely_benign	0.17	benign	-0.283	Destabilizing	None	N	0.381	neutral	None	None	None	None	N
N/M	0.2323	likely_benign	0.25	benign	0.358	Stabilizing	0.214	N	0.542	neutral	None	None	None	None	N
N/P	0.3429	ambiguous	0.4067	ambiguous	-0.399	Destabilizing	0.136	N	0.589	neutral	None	None	None	None	N
N/Q	0.1821	likely_benign	0.2081	benign	-0.616	Destabilizing	0.038	N	0.491	neutral	None	None	None	None	N
N/R	0.1678	likely_benign	0.1896	benign	0.18	Stabilizing	0.038	N	0.385	neutral	None	None	None	None	N
N/S	0.0676	likely_benign	0.0702	benign	-0.339	Destabilizing	0.012	N	0.347	neutral	N	0.408188893	None	None	N
N/T	0.0922	likely_benign	0.0969	benign	-0.202	Destabilizing	None	N	0.143	neutral	N	0.41301871	None	None	N
N/V	0.1264	likely_benign	0.1386	benign	-0.399	Destabilizing	0.001	N	0.383	neutral	None	None	None	None	N
N/W	0.5982	likely_pathogenic	0.6562	pathogenic	-0.893	Destabilizing	0.864	D	0.542	neutral	None	None	None	None	N
N/Y	0.1127	likely_benign	0.1273	benign	-0.654	Destabilizing	0.295	N	0.551	neutral	N	0.453964042	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.