TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31182	93769;93770;93771	chr2:178548082;178548081;178548080	chr2:179412809;179412808;179412807
N2AB	29541	88846;88847;88848	chr2:178548082;178548081;178548080	chr2:179412809;179412808;179412807
N2A	28614	86065;86066;86067	chr2:178548082;178548081;178548080	chr2:179412809;179412808;179412807
N2B	22117	66574;66575;66576	chr2:178548082;178548081;178548080	chr2:179412809;179412808;179412807
Novex-1	22242	66949;66950;66951	chr2:178548082;178548081;178548080	chr2:179412809;179412808;179412807
Novex-2	22309	67150;67151;67152	chr2:178548082;178548081;178548080	chr2:179412809;179412808;179412807
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: Fn3-115
• Domain position: 70
• Structural Position: 104
• Q(SASA): 0.0839
• 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	1.0	D	0.862	0.881	0.850711299093	gnomAD-4.0.0	1.59109E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85802E-06	0	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	0.9771	likely_pathogenic	0.9764	pathogenic	-3.149	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
Y/C	0.8113	likely_pathogenic	0.8307	pathogenic	-1.953	Destabilizing	1.0	D	0.862	deleterious	D	0.647397783	None	None	N
Y/D	0.9886	likely_pathogenic	0.9844	pathogenic	-3.522	Highly Destabilizing	1.0	D	0.867	deleterious	D	0.672935895	None	None	N
Y/E	0.995	likely_pathogenic	0.9942	pathogenic	-3.324	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
Y/F	0.2568	likely_benign	0.2618	benign	-1.134	Destabilizing	0.999	D	0.757	deleterious	D	0.611453341	None	None	N
Y/G	0.9653	likely_pathogenic	0.9599	pathogenic	-3.566	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
Y/H	0.9344	likely_pathogenic	0.9264	pathogenic	-2.09	Highly Destabilizing	1.0	D	0.84	deleterious	D	0.656916534	None	None	N
Y/I	0.9158	likely_pathogenic	0.9206	pathogenic	-1.764	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
Y/K	0.994	likely_pathogenic	0.9926	pathogenic	-2.39	Highly Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
Y/L	0.85	likely_pathogenic	0.858	pathogenic	-1.764	Destabilizing	0.999	D	0.816	deleterious	None	None	None	None	N
Y/M	0.9134	likely_pathogenic	0.9063	pathogenic	-1.497	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
Y/N	0.9164	likely_pathogenic	0.8998	pathogenic	-3.182	Highly Destabilizing	1.0	D	0.863	deleterious	D	0.67273409	None	None	N
Y/P	0.9991	likely_pathogenic	0.9988	pathogenic	-2.241	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
Y/Q	0.9904	likely_pathogenic	0.9894	pathogenic	-2.944	Highly Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
Y/R	0.9845	likely_pathogenic	0.9821	pathogenic	-2.085	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
Y/S	0.9627	likely_pathogenic	0.9564	pathogenic	-3.529	Highly Destabilizing	1.0	D	0.878	deleterious	D	0.672935895	None	None	N
Y/T	0.9757	likely_pathogenic	0.9738	pathogenic	-3.213	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
Y/V	0.8486	likely_pathogenic	0.8541	pathogenic	-2.241	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
Y/W	0.774	likely_pathogenic	0.7456	pathogenic	-0.478	Destabilizing	1.0	D	0.821	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.