TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28623	86092;86093;86094	chr2:178560265;178560264;178560263	chr2:179424992;179424991;179424990
N2AB	26982	81169;81170;81171	chr2:178560265;178560264;178560263	chr2:179424992;179424991;179424990
N2A	26055	78388;78389;78390	chr2:178560265;178560264;178560263	chr2:179424992;179424991;179424990
N2B	19558	58897;58898;58899	chr2:178560265;178560264;178560263	chr2:179424992;179424991;179424990
Novex-1	19683	59272;59273;59274	chr2:178560265;178560264;178560263	chr2:179424992;179424991;179424990
Novex-2	19750	59473;59474;59475	chr2:178560265;178560264;178560263	chr2:179424992;179424991;179424990
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-96
• Domain position: 74
• Structural Position: 106
• Q(SASA): 0.1084
• 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
Y/C	None	None	0.999	N	0.849	0.394	0.582605312856	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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
Y/A	0.9898	likely_pathogenic	0.9811	pathogenic	-3.001	Highly Destabilizing	0.976	D	0.849	deleterious	None	None	None	None	N
Y/C	0.8092	likely_pathogenic	0.5981	pathogenic	-1.586	Destabilizing	0.999	D	0.849	deleterious	N	0.47515422	None	None	N
Y/D	0.9903	likely_pathogenic	0.9837	pathogenic	-3.673	Highly Destabilizing	0.997	D	0.864	deleterious	N	0.487182088	None	None	N
Y/E	0.998	likely_pathogenic	0.9961	pathogenic	-3.453	Highly Destabilizing	0.998	D	0.866	deleterious	None	None	None	None	N
Y/F	0.1104	likely_benign	0.0994	benign	-1.243	Destabilizing	0.046	N	0.196	neutral	N	0.300292558	None	None	N
Y/G	0.9774	likely_pathogenic	0.9652	pathogenic	-3.41	Highly Destabilizing	0.993	D	0.869	deleterious	None	None	None	None	N
Y/H	0.9511	likely_pathogenic	0.8244	pathogenic	-2.22	Highly Destabilizing	0.997	D	0.713	prob.delet.	N	0.516076002	None	None	N
Y/I	0.926	likely_pathogenic	0.886	pathogenic	-1.625	Destabilizing	0.973	D	0.816	deleterious	None	None	None	None	N
Y/K	0.9982	likely_pathogenic	0.9967	pathogenic	-2.406	Highly Destabilizing	0.998	D	0.868	deleterious	None	None	None	None	N
Y/L	0.9011	likely_pathogenic	0.8594	pathogenic	-1.625	Destabilizing	0.91	D	0.815	deleterious	None	None	None	None	N
Y/M	0.9498	likely_pathogenic	0.9185	pathogenic	-1.256	Destabilizing	0.998	D	0.799	deleterious	None	None	None	None	N
Y/N	0.9651	likely_pathogenic	0.9117	pathogenic	-3.333	Highly Destabilizing	0.997	D	0.862	deleterious	N	0.487182088	None	None	N
Y/P	0.9987	likely_pathogenic	0.9981	pathogenic	-2.101	Highly Destabilizing	0.998	D	0.891	deleterious	None	None	None	None	N
Y/Q	0.9972	likely_pathogenic	0.9922	pathogenic	-3.016	Highly Destabilizing	0.998	D	0.796	deleterious	None	None	None	None	N
Y/R	0.9965	likely_pathogenic	0.9934	pathogenic	-2.305	Highly Destabilizing	0.998	D	0.865	deleterious	None	None	None	None	N
Y/S	0.9791	likely_pathogenic	0.9564	pathogenic	-3.565	Highly Destabilizing	0.991	D	0.863	deleterious	N	0.486675109	None	None	N
Y/T	0.9906	likely_pathogenic	0.9821	pathogenic	-3.223	Highly Destabilizing	0.993	D	0.866	deleterious	None	None	None	None	N
Y/V	0.9095	likely_pathogenic	0.8657	pathogenic	-2.101	Highly Destabilizing	0.953	D	0.804	deleterious	None	None	None	None	N
Y/W	0.7772	likely_pathogenic	0.7019	pathogenic	-0.578	Destabilizing	0.999	D	0.727	prob.delet.	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.