TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27041	81346;81347;81348	chr2:178565011;178565010;178565009	chr2:179429738;179429737;179429736
N2AB	25400	76423;76424;76425	chr2:178565011;178565010;178565009	chr2:179429738;179429737;179429736
N2A	24473	73642;73643;73644	chr2:178565011;178565010;178565009	chr2:179429738;179429737;179429736
N2B	17976	54151;54152;54153	chr2:178565011;178565010;178565009	chr2:179429738;179429737;179429736
Novex-1	18101	54526;54527;54528	chr2:178565011;178565010;178565009	chr2:179429738;179429737;179429736
Novex-2	18168	54727;54728;54729	chr2:178565011;178565010;178565009	chr2:179429738;179429737;179429736
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACG
• RefSeq wild type template codon: TGC
• Domain: Fn3-84
• Domain position: 70
• Structural Position: 102
• Q(SASA): 0.1866
• 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
T/M	rs755178087	-0.239	0.702	N	0.448	0.188	0.361360026772	gnomAD-2.1.1	1.79E-05	None	None	None	None	N	None	0	0	None	0	1.02648E-04	None	0	None	0	2.35E-05	0
T/M	rs755178087	-0.239	0.702	N	0.448	0.188	0.361360026772	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.93573E-04	None	0	0	0	0	0
T/M	rs755178087	-0.239	0.702	N	0.448	0.188	0.361360026772	gnomAD-4.0.0	6.19947E-06	None	None	None	None	N	None	0	0	None	0	4.45931E-05	None	0	0	5.0867E-06	1.09992E-05	1.60149E-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
T/A	0.0658	likely_benign	0.0662	benign	-1.05	Destabilizing	None	N	0.059	neutral	N	0.477736618	None	None	N
T/C	0.182	likely_benign	0.1853	benign	-0.688	Destabilizing	None	N	0.239	neutral	None	None	None	None	N
T/D	0.3796	ambiguous	0.3303	benign	-0.614	Destabilizing	0.038	N	0.389	neutral	None	None	None	None	N
T/E	0.3055	likely_benign	0.2651	benign	-0.52	Destabilizing	0.038	N	0.399	neutral	None	None	None	None	N
T/F	0.2032	likely_benign	0.1792	benign	-0.853	Destabilizing	0.356	N	0.5	neutral	None	None	None	None	N
T/G	0.1691	likely_benign	0.171	benign	-1.4	Destabilizing	0.016	N	0.333	neutral	None	None	None	None	N
T/H	0.2666	likely_benign	0.226	benign	-1.558	Destabilizing	0.356	N	0.471	neutral	None	None	None	None	N
T/I	0.13	likely_benign	0.1157	benign	-0.176	Destabilizing	0.001	N	0.198	neutral	None	None	None	None	N
T/K	0.2967	likely_benign	0.2362	benign	-0.744	Destabilizing	0.07	N	0.399	neutral	N	0.503403067	None	None	N
T/L	0.0834	likely_benign	0.0788	benign	-0.176	Destabilizing	0.007	N	0.293	neutral	None	None	None	None	N
T/M	0.0755	likely_benign	0.072	benign	-0.014	Destabilizing	0.702	D	0.448	neutral	N	0.476708972	None	None	N
T/N	0.1012	likely_benign	0.0959	benign	-1.005	Destabilizing	0.038	N	0.355	neutral	None	None	None	None	N
T/P	0.7246	likely_pathogenic	0.662	pathogenic	-0.434	Destabilizing	0.055	N	0.472	neutral	D	0.523819715	None	None	N
T/Q	0.2314	likely_benign	0.1977	benign	-0.992	Destabilizing	0.214	N	0.475	neutral	None	None	None	None	N
T/R	0.2541	likely_benign	0.2002	benign	-0.678	Destabilizing	0.13	N	0.479	neutral	N	0.510078323	None	None	N
T/S	0.0807	likely_benign	0.0813	benign	-1.306	Destabilizing	None	N	0.061	neutral	N	0.475408389	None	None	N
T/V	0.0987	likely_benign	0.0907	benign	-0.434	Destabilizing	None	N	0.087	neutral	None	None	None	None	N
T/W	0.5401	ambiguous	0.5038	ambiguous	-0.84	Destabilizing	0.864	D	0.448	neutral	None	None	None	None	N
T/Y	0.2294	likely_benign	0.2097	benign	-0.565	Destabilizing	0.356	N	0.499	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.