TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29330	88213;88214;88215	chr2:178557274;178557273;178557272	chr2:179422001;179422000;179421999
N2AB	27689	83290;83291;83292	chr2:178557274;178557273;178557272	chr2:179422001;179422000;179421999
N2A	26762	80509;80510;80511	chr2:178557274;178557273;178557272	chr2:179422001;179422000;179421999
N2B	20265	61018;61019;61020	chr2:178557274;178557273;178557272	chr2:179422001;179422000;179421999
Novex-1	20390	61393;61394;61395	chr2:178557274;178557273;178557272	chr2:179422001;179422000;179421999
Novex-2	20457	61594;61595;61596	chr2:178557274;178557273;178557272	chr2:179422001;179422000;179421999
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-101
• Domain position: 94
• Structural Position: 127
• Q(SASA): 0.2481
• 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
V/A	rs1701877919	None	0.997	N	0.676	0.333	0.60416271137	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-06	0	3.66327E-05

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
V/A	0.3797	ambiguous	0.3338	benign	-1.617	Destabilizing	0.997	D	0.676	prob.neutral	N	0.480733173	None	None	N
V/C	0.7513	likely_pathogenic	0.7421	pathogenic	-1.049	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
V/D	0.9219	likely_pathogenic	0.9115	pathogenic	-1.574	Destabilizing	0.999	D	0.851	deleterious	N	0.508245177	None	None	N
V/E	0.7646	likely_pathogenic	0.715	pathogenic	-1.42	Destabilizing	0.999	D	0.887	deleterious	None	None	None	None	N
V/F	0.3225	likely_benign	0.2939	benign	-0.972	Destabilizing	0.999	D	0.865	deleterious	N	0.480986662	None	None	N
V/G	0.6205	likely_pathogenic	0.5878	pathogenic	-2.061	Highly Destabilizing	0.999	D	0.857	deleterious	N	0.508245177	None	None	N
V/H	0.8582	likely_pathogenic	0.8397	pathogenic	-1.489	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
V/I	0.0899	likely_benign	0.0914	benign	-0.424	Destabilizing	0.994	D	0.623	neutral	N	0.47670675	None	None	N
V/K	0.7716	likely_pathogenic	0.7286	pathogenic	-1.324	Destabilizing	0.999	D	0.889	deleterious	None	None	None	None	N
V/L	0.3146	likely_benign	0.3141	benign	-0.424	Destabilizing	0.994	D	0.64	neutral	N	0.466717068	None	None	N
V/M	0.2107	likely_benign	0.2001	benign	-0.404	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
V/N	0.7666	likely_pathogenic	0.7504	pathogenic	-1.489	Destabilizing	0.999	D	0.834	deleterious	None	None	None	None	N
V/P	0.981	likely_pathogenic	0.9843	pathogenic	-0.791	Destabilizing	0.999	D	0.881	deleterious	None	None	None	None	N
V/Q	0.6393	likely_pathogenic	0.5966	pathogenic	-1.413	Destabilizing	0.999	D	0.861	deleterious	None	None	None	None	N
V/R	0.7008	likely_pathogenic	0.6489	pathogenic	-1.065	Destabilizing	0.999	D	0.845	deleterious	None	None	None	None	N
V/S	0.5545	ambiguous	0.514	ambiguous	-2.099	Highly Destabilizing	0.999	D	0.879	deleterious	None	None	None	None	N
V/T	0.3425	ambiguous	0.3028	benign	-1.801	Destabilizing	0.998	D	0.633	neutral	None	None	None	None	N
V/W	0.9467	likely_pathogenic	0.9424	pathogenic	-1.307	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
V/Y	0.786	likely_pathogenic	0.7681	pathogenic	-0.925	Destabilizing	0.999	D	0.851	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.