TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9964	30115;30116;30117	chr2:178704582;178704581;178704580	chr2:179569309;179569308;179569307
N2AB	9647	29164;29165;29166	chr2:178704582;178704581;178704580	chr2:179569309;179569308;179569307
N2A	8720	26383;26384;26385	chr2:178704582;178704581;178704580	chr2:179569309;179569308;179569307
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: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Ig-84
• Domain position: 65
• Structural Position: 145
• Q(SASA): 0.123
• 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
Q/P	None	None	0.999	None	0.467	0.587	0.52674250279	gnomAD-4.0.0	1.59238E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88359E-05	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
Q/A	0.3248	likely_benign	0.3551	ambiguous	-0.293	Destabilizing	0.964	D	0.489	neutral	None	None	None	None	N
Q/C	0.7599	likely_pathogenic	0.7778	pathogenic	0.178	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
Q/D	0.4889	ambiguous	0.5018	ambiguous	-1.235	Destabilizing	0.993	D	0.419	neutral	None	None	None	None	N
Q/E	0.1092	likely_benign	0.1066	benign	-1.153	Destabilizing	0.977	D	0.419	neutral	None	None	None	None	N
Q/F	0.7756	likely_pathogenic	0.7765	pathogenic	-0.185	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
Q/G	0.4195	ambiguous	0.4186	ambiguous	-0.639	Destabilizing	0.993	D	0.503	neutral	None	None	None	None	N
Q/H	0.2763	likely_benign	0.2817	benign	-0.815	Destabilizing	0.999	D	0.43	neutral	None	None	None	None	N
Q/I	0.5122	ambiguous	0.5556	ambiguous	0.578	Stabilizing	0.996	D	0.667	neutral	None	None	None	None	N
Q/K	0.1174	likely_benign	0.1213	benign	-0.375	Destabilizing	0.99	D	0.462	neutral	None	None	None	None	N
Q/L	0.1906	likely_benign	0.1901	benign	0.578	Stabilizing	0.98	D	0.501	neutral	None	None	None	None	N
Q/M	0.4894	ambiguous	0.5071	ambiguous	1.161	Stabilizing	0.999	D	0.43	neutral	None	None	None	None	N
Q/N	0.3539	ambiguous	0.3547	ambiguous	-0.954	Destabilizing	0.993	D	0.413	neutral	None	None	None	None	N
Q/P	0.5981	likely_pathogenic	0.5834	pathogenic	0.32	Stabilizing	0.999	D	0.467	neutral	None	None	None	None	N
Q/R	0.1379	likely_benign	0.1389	benign	-0.336	Destabilizing	0.99	D	0.473	neutral	None	None	None	None	N
Q/S	0.3177	likely_benign	0.3295	benign	-0.902	Destabilizing	0.971	D	0.439	neutral	None	None	None	None	N
Q/T	0.2798	likely_benign	0.2919	benign	-0.645	Destabilizing	0.469	N	0.23	neutral	None	None	None	None	N
Q/V	0.3663	ambiguous	0.4063	ambiguous	0.32	Stabilizing	0.985	D	0.501	neutral	None	None	None	None	N
Q/W	0.7835	likely_pathogenic	0.7793	pathogenic	-0.228	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
Q/Y	0.6456	likely_pathogenic	0.6464	pathogenic	0.086	Stabilizing	0.999	D	0.509	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.