TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6361	19306;19307;19308	chr2:178728957;178728956;178728955	chr2:179593684;179593683;179593682
N2AB	6044	18355;18356;18357	chr2:178728957;178728956;178728955	chr2:179593684;179593683;179593682
N2A	5117	15574;15575;15576	chr2:178728957;178728956;178728955	chr2:179593684;179593683;179593682
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-47
• Domain position: 70
• Structural Position: 153
• Q(SASA): 0.3673
• 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
R/S	None	None	0.92	N	0.495	0.34	0.273503213844	gnomAD-4.0.0	1.59354E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43542E-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
R/A	0.6471	likely_pathogenic	0.5592	ambiguous	-1.669	Destabilizing	0.863	D	0.476	neutral	None	None	None	None	N
R/C	0.3215	likely_benign	0.2749	benign	-1.45	Destabilizing	0.999	D	0.633	neutral	None	None	None	None	N
R/D	0.8503	likely_pathogenic	0.7794	pathogenic	-0.318	Destabilizing	0.884	D	0.561	neutral	None	None	None	None	N
R/E	0.5225	ambiguous	0.4645	ambiguous	-0.131	Destabilizing	0.17	N	0.185	neutral	None	None	None	None	N
R/F	0.6646	likely_pathogenic	0.5675	pathogenic	-1.178	Destabilizing	0.997	D	0.627	neutral	None	None	None	None	N
R/G	0.5425	ambiguous	0.4518	ambiguous	-2.023	Highly Destabilizing	0.959	D	0.559	neutral	N	0.490745666	None	None	N
R/H	0.1352	likely_benign	0.1179	benign	-2.042	Highly Destabilizing	0.997	D	0.541	neutral	None	None	None	None	N
R/I	0.334	likely_benign	0.273	benign	-0.67	Destabilizing	0.996	D	0.642	neutral	N	0.476819472	None	None	N
R/K	0.1226	likely_benign	0.1156	benign	-1.134	Destabilizing	0.061	N	0.165	neutral	N	0.385850751	None	None	N
R/L	0.3536	ambiguous	0.2887	benign	-0.67	Destabilizing	0.969	D	0.557	neutral	None	None	None	None	N
R/M	0.4006	ambiguous	0.3393	benign	-0.983	Destabilizing	0.997	D	0.585	neutral	None	None	None	None	N
R/N	0.7038	likely_pathogenic	0.6137	pathogenic	-0.822	Destabilizing	0.969	D	0.459	neutral	None	None	None	None	N
R/P	0.863	likely_pathogenic	0.7953	pathogenic	-0.987	Destabilizing	0.997	D	0.636	neutral	None	None	None	None	N
R/Q	0.1388	likely_benign	0.1252	benign	-0.895	Destabilizing	0.939	D	0.447	neutral	None	None	None	None	N
R/S	0.6849	likely_pathogenic	0.5901	pathogenic	-1.835	Destabilizing	0.92	D	0.495	neutral	N	0.477472833	None	None	N
R/T	0.4184	ambiguous	0.3334	benign	-1.429	Destabilizing	0.959	D	0.479	neutral	N	0.438493158	None	None	N
R/V	0.4829	ambiguous	0.4186	ambiguous	-0.987	Destabilizing	0.969	D	0.616	neutral	None	None	None	None	N
R/W	0.2594	likely_benign	0.2146	benign	-0.633	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	N
R/Y	0.4619	ambiguous	0.384	ambiguous	-0.469	Destabilizing	0.997	D	0.643	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.