TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30326	91201;91202;91203	chr2:178551924;178551923;178551922	chr2:179416651;179416650;179416649
N2AB	28685	86278;86279;86280	chr2:178551924;178551923;178551922	chr2:179416651;179416650;179416649
N2A	27758	83497;83498;83499	chr2:178551924;178551923;178551922	chr2:179416651;179416650;179416649
N2B	21261	64006;64007;64008	chr2:178551924;178551923;178551922	chr2:179416651;179416650;179416649
Novex-1	21386	64381;64382;64383	chr2:178551924;178551923;178551922	chr2:179416651;179416650;179416649
Novex-2	21453	64582;64583;64584	chr2:178551924;178551923;178551922	chr2:179416651;179416650;179416649
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-109
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.2209
• 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
G/V	rs1193099278	-0.038	1.0	N	0.843	0.48	0.774184965001	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	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
G/A	0.2242	likely_benign	0.3112	benign	-0.823	Destabilizing	1.0	D	0.659	neutral	N	0.481052795	None	None	N
G/C	0.462	ambiguous	0.5997	pathogenic	-1.25	Destabilizing	1.0	D	0.774	deleterious	N	0.519035732	None	None	N
G/D	0.7482	likely_pathogenic	0.8076	pathogenic	-1.674	Destabilizing	1.0	D	0.803	deleterious	N	0.490598767	None	None	N
G/E	0.7099	likely_pathogenic	0.7906	pathogenic	-1.694	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
G/F	0.8189	likely_pathogenic	0.9045	pathogenic	-1.077	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
G/H	0.8103	likely_pathogenic	0.891	pathogenic	-1.346	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
G/I	0.7094	likely_pathogenic	0.8468	pathogenic	-0.383	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
G/K	0.8633	likely_pathogenic	0.9208	pathogenic	-1.188	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
G/L	0.6891	likely_pathogenic	0.8066	pathogenic	-0.383	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
G/M	0.7707	likely_pathogenic	0.8617	pathogenic	-0.508	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
G/N	0.7003	likely_pathogenic	0.7688	pathogenic	-1.041	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
G/P	0.9756	likely_pathogenic	0.9853	pathogenic	-0.49	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
G/Q	0.7344	likely_pathogenic	0.8266	pathogenic	-1.221	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
G/R	0.7827	likely_pathogenic	0.8717	pathogenic	-0.949	Destabilizing	1.0	D	0.825	deleterious	N	0.488307724	None	None	N
G/S	0.1503	likely_benign	0.1915	benign	-1.306	Destabilizing	1.0	D	0.713	prob.delet.	N	0.504871999	None	None	N
G/T	0.4462	ambiguous	0.5551	ambiguous	-1.251	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
G/V	0.5846	likely_pathogenic	0.757	pathogenic	-0.49	Destabilizing	1.0	D	0.843	deleterious	N	0.500677987	None	None	N
G/W	0.808	likely_pathogenic	0.8941	pathogenic	-1.443	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
G/Y	0.744	likely_pathogenic	0.8693	pathogenic	-1.013	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.