TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5699	17320;17321;17322	chr2:178731780;178731779;178731778	chr2:179596507;179596506;179596505
N2AB	5382	16369;16370;16371	chr2:178731780;178731779;178731778	chr2:179596507;179596506;179596505
N2A	4455	13588;13589;13590	chr2:178731780;178731779;178731778	chr2:179596507;179596506;179596505
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: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-40
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.0844
• 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
F/S	rs929174376	None	0.997	N	0.646	0.545	0.883764784581	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
F/S	rs929174376	None	0.997	N	0.646	0.545	0.883764784581	gnomAD-4.0.0	6.57419E-06	None	None	None	None	N	None	0	6.55222E-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
F/A	0.6235	likely_pathogenic	0.6194	pathogenic	-3.554	Highly Destabilizing	0.985	D	0.547	neutral	None	None	None	None	N
F/C	0.3269	likely_benign	0.3226	benign	-2.466	Highly Destabilizing	1.0	D	0.631	neutral	N	0.483014726	None	None	N
F/D	0.9819	likely_pathogenic	0.9752	pathogenic	-3.811	Highly Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
F/E	0.9817	likely_pathogenic	0.9769	pathogenic	-3.632	Highly Destabilizing	0.999	D	0.69	prob.neutral	None	None	None	None	N
F/G	0.8798	likely_pathogenic	0.8686	pathogenic	-3.943	Highly Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
F/H	0.9301	likely_pathogenic	0.9214	pathogenic	-2.296	Highly Destabilizing	1.0	D	0.631	neutral	None	None	None	None	N
F/I	0.3448	ambiguous	0.3255	benign	-2.262	Highly Destabilizing	0.961	D	0.536	neutral	N	0.449051294	None	None	N
F/K	0.9905	likely_pathogenic	0.987	pathogenic	-2.396	Highly Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
F/L	0.9005	likely_pathogenic	0.9038	pathogenic	-2.262	Highly Destabilizing	0.135	N	0.308	neutral	N	0.404879229	None	None	N
F/M	0.6023	likely_pathogenic	0.6189	pathogenic	-2.121	Highly Destabilizing	0.996	D	0.593	neutral	None	None	None	None	N
F/N	0.8935	likely_pathogenic	0.884	pathogenic	-2.778	Highly Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
F/P	0.9827	likely_pathogenic	0.9716	pathogenic	-2.707	Highly Destabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	N
F/Q	0.9754	likely_pathogenic	0.9706	pathogenic	-2.836	Highly Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	N
F/R	0.9767	likely_pathogenic	0.9708	pathogenic	-1.718	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
F/S	0.6895	likely_pathogenic	0.6837	pathogenic	-3.408	Highly Destabilizing	0.997	D	0.646	neutral	N	0.499637617	None	None	N
F/T	0.6346	likely_pathogenic	0.6325	pathogenic	-3.128	Highly Destabilizing	0.985	D	0.635	neutral	None	None	None	None	N
F/V	0.2657	likely_benign	0.2635	benign	-2.707	Highly Destabilizing	0.4	N	0.453	neutral	N	0.389538844	None	None	N
F/W	0.8063	likely_pathogenic	0.7788	pathogenic	-0.826	Destabilizing	1.0	D	0.596	neutral	None	None	None	None	N
F/Y	0.2935	likely_benign	0.2799	benign	-1.342	Destabilizing	0.997	D	0.567	neutral	N	0.494175479	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.