TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21335	64228;64229;64230	chr2:178587208;178587207;178587206	chr2:179451935;179451934;179451933
N2AB	19694	59305;59306;59307	chr2:178587208;178587207;178587206	chr2:179451935;179451934;179451933
N2A	18767	56524;56525;56526	chr2:178587208;178587207;178587206	chr2:179451935;179451934;179451933
N2B	12270	37033;37034;37035	chr2:178587208;178587207;178587206	chr2:179451935;179451934;179451933
Novex-1	12395	37408;37409;37410	chr2:178587208;178587207;178587206	chr2:179451935;179451934;179451933
Novex-2	12462	37609;37610;37611	chr2:178587208;178587207;178587206	chr2:179451935;179451934;179451933
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-42
• Domain position: 70
• Structural Position: 103
• Q(SASA): 0.4716
• 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
E/K	rs773791222	-0.918	0.999	N	0.592	0.362	None	gnomAD-2.1.1	2.14E-05	None	None	None	None	N	None	2.06731E-04	0	None	0	0	None	0	None	0	7.82E-06	0
E/K	rs773791222	-0.918	0.999	N	0.592	0.362	None	gnomAD-3.1.2	5.26E-05	None	None	None	None	N	None	1.93181E-04	0	0	0	0	None	0	0	0	0	0
E/K	rs773791222	-0.918	0.999	N	0.592	0.362	None	gnomAD-4.0.0	1.11583E-05	None	None	None	None	N	None	1.87056E-04	0	None	0	0	None	0	0	1.69566E-06	0	3.2041E-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
E/A	0.1612	likely_benign	0.1404	benign	-1.029	Destabilizing	0.999	D	0.699	prob.neutral	D	0.5246582	None	None	N
E/C	0.7988	likely_pathogenic	0.7707	pathogenic	-0.549	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/D	0.1896	likely_benign	0.2098	benign	-1.271	Destabilizing	0.999	D	0.475	neutral	N	0.486601244	None	None	N
E/F	0.7974	likely_pathogenic	0.7649	pathogenic	-0.298	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/G	0.2565	likely_benign	0.228	benign	-1.463	Destabilizing	1.0	D	0.761	deleterious	N	0.475638427	None	None	N
E/H	0.5227	ambiguous	0.4596	ambiguous	-0.635	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
E/I	0.3485	ambiguous	0.3359	benign	0.189	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
E/K	0.2098	likely_benign	0.1668	benign	-0.98	Destabilizing	0.999	D	0.592	neutral	N	0.487177247	None	None	N
E/L	0.4285	ambiguous	0.3929	ambiguous	0.189	Stabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
E/M	0.4545	ambiguous	0.4282	ambiguous	0.827	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/N	0.3116	likely_benign	0.3073	benign	-1.466	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
E/P	0.5939	likely_pathogenic	0.5451	ambiguous	-0.197	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
E/Q	0.1489	likely_benign	0.1245	benign	-1.255	Destabilizing	1.0	D	0.606	neutral	N	0.516692077	None	None	N
E/R	0.3384	likely_benign	0.2656	benign	-0.709	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
E/S	0.2124	likely_benign	0.1971	benign	-1.939	Destabilizing	0.999	D	0.632	neutral	None	None	None	None	N
E/T	0.2095	likely_benign	0.1975	benign	-1.565	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
E/V	0.2147	likely_benign	0.2057	benign	-0.197	Destabilizing	1.0	D	0.803	deleterious	N	0.516193432	None	None	N
E/W	0.937	likely_pathogenic	0.9218	pathogenic	-0.063	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
E/Y	0.6508	likely_pathogenic	0.6145	pathogenic	-0.044	Destabilizing	1.0	D	0.787	deleterious	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.