TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35367	106324;106325;106326	chr2:178530516;178530515;178530514	chr2:179395243;179395242;179395241
N2AB	33726	101401;101402;101403	chr2:178530516;178530515;178530514	chr2:179395243;179395242;179395241
N2A	32799	98620;98621;98622	chr2:178530516;178530515;178530514	chr2:179395243;179395242;179395241
N2B	26302	79129;79130;79131	chr2:178530516;178530515;178530514	chr2:179395243;179395242;179395241
Novex-1	26427	79504;79505;79506	chr2:178530516;178530515;178530514	chr2:179395243;179395242;179395241
Novex-2	26494	79705;79706;79707	chr2:178530516;178530515;178530514	chr2:179395243;179395242;179395241
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: Ig-165
• Domain position: 82
• Structural Position: 165
• Q(SASA): 0.544
• Predicted PPI site: I

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	rs377056111	-0.02	0.808	N	0.461	0.138	None	gnomAD-2.1.1	4.28E-05	None	None	None	None	I	None	4.13E-05	2.83E-05	None	0	0	None	3.27E-05	None	1.59936E-04	3.12E-05	1.40252E-04
T/M	rs377056111	-0.02	0.808	N	0.461	0.138	None	gnomAD-3.1.2	4.6E-05	None	None	None	None	I	None	2.41E-05	6.54E-05	0	0	0	None	1.8875E-04	0	4.41E-05	0	0
T/M	rs377056111	-0.02	0.808	N	0.461	0.138	None	gnomAD-4.0.0	1.10918E-04	None	None	None	None	I	None	5.34131E-05	1.66639E-05	None	0	2.22737E-05	None	3.28197E-04	0	1.24588E-04	1.09803E-05	6.40369E-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	0.0807	likely_benign	0.0861	benign	-0.548	Destabilizing	None	N	0.105	neutral	N	0.46829599	None	None	I
T/C	0.367	ambiguous	0.3893	ambiguous	-0.275	Destabilizing	0.667	D	0.469	neutral	None	None	None	None	I
T/D	0.3421	ambiguous	0.3404	ambiguous	0.154	Stabilizing	0.124	N	0.381	neutral	None	None	None	None	I
T/E	0.294	likely_benign	0.2896	benign	0.07	Stabilizing	0.002	N	0.201	neutral	None	None	None	None	I
T/F	0.1913	likely_benign	0.1868	benign	-1.066	Destabilizing	0.497	N	0.501	neutral	None	None	None	None	I
T/G	0.2461	likely_benign	0.2611	benign	-0.664	Destabilizing	0.055	N	0.446	neutral	None	None	None	None	I
T/H	0.2446	likely_benign	0.2298	benign	-1.005	Destabilizing	0.859	D	0.487	neutral	None	None	None	None	I
T/I	0.11	likely_benign	0.1097	benign	-0.359	Destabilizing	None	N	0.185	neutral	None	None	None	None	I
T/K	0.1829	likely_benign	0.1706	benign	-0.367	Destabilizing	0.351	N	0.376	neutral	N	0.468311845	None	None	I
T/L	0.105	likely_benign	0.106	benign	-0.359	Destabilizing	0.025	N	0.279	neutral	None	None	None	None	I
T/M	0.1026	likely_benign	0.1033	benign	-0.009	Destabilizing	0.808	D	0.461	neutral	N	0.516012579	None	None	I
T/N	0.1183	likely_benign	0.1161	benign	-0.101	Destabilizing	0.364	N	0.376	neutral	None	None	None	None	I
T/P	0.16	likely_benign	0.1674	benign	-0.395	Destabilizing	0.301	N	0.47	neutral	D	0.524728062	None	None	I
T/Q	0.2315	likely_benign	0.2209	benign	-0.397	Destabilizing	0.22	N	0.459	neutral	None	None	None	None	I
T/R	0.1519	likely_benign	0.1401	benign	-0.081	Destabilizing	0.351	N	0.455	neutral	N	0.490999491	None	None	I
T/S	0.1073	likely_benign	0.1095	benign	-0.355	Destabilizing	0.042	N	0.28	neutral	N	0.451902385	None	None	I
T/V	0.1095	likely_benign	0.1139	benign	-0.395	Destabilizing	None	N	0.121	neutral	None	None	None	None	I
T/W	0.5857	likely_pathogenic	0.566	pathogenic	-1.009	Destabilizing	0.958	D	0.489	neutral	None	None	None	None	I
T/Y	0.2692	likely_benign	0.2565	benign	-0.747	Destabilizing	0.859	D	0.494	neutral	None	None	None	None	I

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.