TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9483	28672;28673;28674	chr2:178710650;178710649;178710648	chr2:179575377;179575376;179575375
N2AB	9166	27721;27722;27723	chr2:178710650;178710649;178710648	chr2:179575377;179575376;179575375
N2A	8239	24940;24941;24942	chr2:178710650;178710649;178710648	chr2:179575377;179575376;179575375
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: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-80
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.2889
• 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
Q/R	None	None	0.326	None	0.366	0.139	0.24896430686	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
Q/A	0.1834	likely_benign	0.2063	benign	-0.739	Destabilizing	0.209	N	0.311	neutral	None	None	None	None	N
Q/C	0.7293	likely_pathogenic	0.7537	pathogenic	-0.163	Destabilizing	0.991	D	0.559	neutral	None	None	None	None	N
Q/D	0.297	likely_benign	0.3338	benign	-0.768	Destabilizing	0.002	N	0.159	neutral	None	None	None	None	N
Q/E	0.0992	likely_benign	0.0865	benign	-0.641	Destabilizing	0.005	N	0.127	neutral	None	None	None	None	N
Q/F	0.5189	ambiguous	0.5685	pathogenic	-0.417	Destabilizing	0.901	D	0.578	neutral	None	None	None	None	N
Q/G	0.2833	likely_benign	0.3478	ambiguous	-1.119	Destabilizing	0.345	N	0.427	neutral	None	None	None	None	N
Q/H	0.1721	likely_benign	0.1922	benign	-0.932	Destabilizing	0.873	D	0.503	neutral	None	None	None	None	N
Q/I	0.2876	likely_benign	0.2904	benign	0.243	Stabilizing	0.39	N	0.569	neutral	None	None	None	None	N
Q/K	0.1036	likely_benign	0.1062	benign	-0.334	Destabilizing	0.001	N	0.147	neutral	None	None	None	None	N
Q/L	0.1323	likely_benign	0.1231	benign	0.243	Stabilizing	0.166	N	0.44	neutral	None	None	None	None	N
Q/M	0.3103	likely_benign	0.3214	benign	0.673	Stabilizing	0.901	D	0.509	neutral	None	None	None	None	N
Q/N	0.2154	likely_benign	0.2452	benign	-1.007	Destabilizing	0.017	N	0.163	neutral	None	None	None	None	N
Q/P	0.1333	likely_benign	0.1554	benign	-0.053	Destabilizing	0.003	N	0.213	neutral	None	None	None	None	N
Q/R	0.1186	likely_benign	0.1265	benign	-0.304	Destabilizing	0.326	N	0.366	neutral	None	None	None	None	N
Q/S	0.1704	likely_benign	0.2259	benign	-1.125	Destabilizing	0.345	N	0.303	neutral	None	None	None	None	N
Q/T	0.154	likely_benign	0.1776	benign	-0.791	Destabilizing	0.345	N	0.399	neutral	None	None	None	None	N
Q/V	0.1997	likely_benign	0.2011	benign	-0.053	Destabilizing	0.017	N	0.31	neutral	None	None	None	None	N
Q/W	0.4916	ambiguous	0.5366	ambiguous	-0.282	Destabilizing	0.991	D	0.574	neutral	None	None	None	None	N
Q/Y	0.3824	ambiguous	0.4218	ambiguous	-0.032	Destabilizing	0.965	D	0.596	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.