TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1496	4711;4712;4713	chr2:178777579;178777578;178777577	chr2:179642306;179642305;179642304
N2AB	1496	4711;4712;4713	chr2:178777579;178777578;178777577	chr2:179642306;179642305;179642304
N2A	1496	4711;4712;4713	chr2:178777579;178777578;178777577	chr2:179642306;179642305;179642304
N2B	1450	4573;4574;4575	chr2:178777579;178777578;178777577	chr2:179642306;179642305;179642304
Novex-1	1450	4573;4574;4575	chr2:178777579;178777578;178777577	chr2:179642306;179642305;179642304
Novex-2	1450	4573;4574;4575	chr2:178777579;178777578;178777577	chr2:179642306;179642305;179642304
Novex-3	1496	4711;4712;4713	chr2:178777579;178777578;178777577	chr2:179642306;179642305;179642304

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Ig-6
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.4184
• 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/H	rs1451784393	-0.135	0.999	N	0.597	0.287	0.397540356873	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.63E-05	0	0
Q/H	rs1451784393	-0.135	0.999	N	0.597	0.287	0.397540356873	gnomAD-4.0.0	1.59107E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.8831E-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	0.3727	ambiguous	0.3506	ambiguous	-0.376	Destabilizing	0.997	D	0.559	neutral	None	None	None	None	N
Q/C	0.89	likely_pathogenic	0.8822	pathogenic	-0.113	Destabilizing	1.0	D	0.656	neutral	None	None	None	None	N
Q/D	0.8677	likely_pathogenic	0.8333	pathogenic	0.24	Stabilizing	0.997	D	0.577	neutral	None	None	None	None	N
Q/E	0.1396	likely_benign	0.1311	benign	0.293	Stabilizing	0.992	D	0.46	neutral	N	0.479421384	None	None	N
Q/F	0.9633	likely_pathogenic	0.9536	pathogenic	-0.378	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
Q/G	0.7121	likely_pathogenic	0.6678	pathogenic	-0.626	Destabilizing	0.997	D	0.54	neutral	None	None	None	None	N
Q/H	0.6565	likely_pathogenic	0.5953	pathogenic	-0.171	Destabilizing	0.999	D	0.597	neutral	N	0.51334847	None	None	N
Q/I	0.6762	likely_pathogenic	0.6369	pathogenic	0.22	Stabilizing	0.999	D	0.673	neutral	None	None	None	None	N
Q/K	0.1931	likely_benign	0.1765	benign	0.064	Stabilizing	0.997	D	0.547	neutral	N	0.499416171	None	None	N
Q/L	0.3148	likely_benign	0.289	benign	0.22	Stabilizing	0.997	D	0.54	neutral	N	0.490918293	None	None	N
Q/M	0.5173	ambiguous	0.498	ambiguous	0.154	Stabilizing	0.999	D	0.595	neutral	None	None	None	None	N
Q/N	0.6387	likely_pathogenic	0.5918	pathogenic	-0.508	Destabilizing	0.999	D	0.57	neutral	None	None	None	None	N
Q/P	0.2084	likely_benign	0.1837	benign	0.05	Stabilizing	0.999	D	0.643	neutral	N	0.394942615	None	None	N
Q/R	0.2622	likely_benign	0.2314	benign	0.235	Stabilizing	0.997	D	0.573	neutral	N	0.503163805	None	None	N
Q/S	0.5844	likely_pathogenic	0.5398	ambiguous	-0.59	Destabilizing	0.997	D	0.554	neutral	None	None	None	None	N
Q/T	0.4956	ambiguous	0.4469	ambiguous	-0.357	Destabilizing	0.999	D	0.6	neutral	None	None	None	None	N
Q/V	0.4975	ambiguous	0.4637	ambiguous	0.05	Stabilizing	0.999	D	0.555	neutral	None	None	None	None	N
Q/W	0.9502	likely_pathogenic	0.9368	pathogenic	-0.331	Destabilizing	1.0	D	0.626	neutral	None	None	None	None	N
Q/Y	0.9042	likely_pathogenic	0.8802	pathogenic	-0.063	Destabilizing	0.999	D	0.637	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.