TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20820	62683;62684;62685	chr2:178589267;178589266;178589265	chr2:179453994;179453993;179453992
N2AB	19179	57760;57761;57762	chr2:178589267;178589266;178589265	chr2:179453994;179453993;179453992
N2A	18252	54979;54980;54981	chr2:178589267;178589266;178589265	chr2:179453994;179453993;179453992
N2B	11755	35488;35489;35490	chr2:178589267;178589266;178589265	chr2:179453994;179453993;179453992
Novex-1	11880	35863;35864;35865	chr2:178589267;178589266;178589265	chr2:179453994;179453993;179453992
Novex-2	11947	36064;36065;36066	chr2:178589267;178589266;178589265	chr2:179453994;179453993;179453992
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-122
• Domain position: 52
• Structural Position: 123
• Q(SASA): 0.2815
• 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
I/L	None	None	0.437	D	0.329	0.189	0.478680857624	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
I/M	None	None	0.984	D	0.502	0.305	0.601658297244	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
I/S	rs369446270	-1.926	0.984	N	0.577	0.552	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
I/S	rs369446270	-1.926	0.984	N	0.577	0.552	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/S	rs369446270	-1.926	0.984	N	0.577	0.552	None	gnomAD-4.0.0	6.57713E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47132E-05	0	0
I/T	rs369446270	-1.543	0.896	N	0.529	0.43	0.704783393649	gnomAD-2.1.1	3.93E-05	None	None	None	None	N	None	0	5.66E-05	None	0	0	None	0	None	1.60115E-04	3.9E-05	0
I/T	rs369446270	-1.543	0.896	N	0.529	0.43	0.704783393649	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	4.78469E-04
I/T	rs369446270	-1.543	0.896	N	0.529	0.43	0.704783393649	gnomAD-4.0.0	4.33891E-05	None	None	None	None	N	None	1.33526E-05	6.67223E-05	None	0	0	None	2.031E-04	0	4.15393E-05	0	4.80461E-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
I/A	0.4148	ambiguous	0.4232	ambiguous	-1.757	Destabilizing	0.851	D	0.495	neutral	None	None	None	None	N
I/C	0.8012	likely_pathogenic	0.8336	pathogenic	-1.12	Destabilizing	0.999	D	0.584	neutral	None	None	None	None	N
I/D	0.9521	likely_pathogenic	0.9529	pathogenic	-0.941	Destabilizing	0.996	D	0.671	neutral	None	None	None	None	N
I/E	0.8457	likely_pathogenic	0.8312	pathogenic	-0.86	Destabilizing	0.988	D	0.65	neutral	None	None	None	None	N
I/F	0.2413	likely_benign	0.2579	benign	-1.047	Destabilizing	0.811	D	0.469	neutral	N	0.495584739	None	None	N
I/G	0.8627	likely_pathogenic	0.8626	pathogenic	-2.159	Highly Destabilizing	0.988	D	0.623	neutral	None	None	None	None	N
I/H	0.8372	likely_pathogenic	0.8374	pathogenic	-1.318	Destabilizing	0.988	D	0.689	prob.neutral	None	None	None	None	N
I/K	0.7393	likely_pathogenic	0.7207	pathogenic	-1.138	Destabilizing	0.988	D	0.647	neutral	None	None	None	None	N
I/L	0.1857	likely_benign	0.1894	benign	-0.69	Destabilizing	0.437	N	0.329	neutral	D	0.533616905	None	None	N
I/M	0.1006	likely_benign	0.101	benign	-0.641	Destabilizing	0.984	D	0.502	neutral	D	0.537446644	None	None	N
I/N	0.6863	likely_pathogenic	0.6867	pathogenic	-1.07	Destabilizing	0.995	D	0.683	prob.neutral	N	0.519578024	None	None	N
I/P	0.9274	likely_pathogenic	0.9414	pathogenic	-1.016	Destabilizing	0.996	D	0.683	prob.neutral	None	None	None	None	N
I/Q	0.7346	likely_pathogenic	0.7245	pathogenic	-1.109	Destabilizing	0.996	D	0.686	prob.neutral	None	None	None	None	N
I/R	0.6611	likely_pathogenic	0.6379	pathogenic	-0.704	Destabilizing	0.996	D	0.682	prob.neutral	None	None	None	None	N
I/S	0.5712	likely_pathogenic	0.5642	pathogenic	-1.794	Destabilizing	0.984	D	0.577	neutral	N	0.521121733	None	None	N
I/T	0.2334	likely_benign	0.2267	benign	-1.573	Destabilizing	0.896	D	0.529	neutral	N	0.501687579	None	None	N
I/V	0.1027	likely_benign	0.1007	benign	-1.016	Destabilizing	0.026	N	0.149	neutral	N	0.514065565	None	None	N
I/W	0.8044	likely_pathogenic	0.8058	pathogenic	-1.156	Destabilizing	0.999	D	0.694	prob.neutral	None	None	None	None	N
I/Y	0.6751	likely_pathogenic	0.6882	pathogenic	-0.914	Destabilizing	0.132	N	0.285	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.