TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31972	96139;96140;96141	chr2:178544315;178544314;178544313	chr2:179409042;179409041;179409040
N2AB	30331	91216;91217;91218	chr2:178544315;178544314;178544313	chr2:179409042;179409041;179409040
N2A	29404	88435;88436;88437	chr2:178544315;178544314;178544313	chr2:179409042;179409041;179409040
N2B	22907	68944;68945;68946	chr2:178544315;178544314;178544313	chr2:179409042;179409041;179409040
Novex-1	23032	69319;69320;69321	chr2:178544315;178544314;178544313	chr2:179409042;179409041;179409040
Novex-2	23099	69520;69521;69522	chr2:178544315;178544314;178544313	chr2:179409042;179409041;179409040
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-121
• Domain position: 64
• Structural Position: 93
• Q(SASA): 0.0843
• 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/M	rs745900975	0.041	0.999	N	0.703	0.419	0.552408913969	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
V/M	rs745900975	0.041	0.999	N	0.703	0.419	0.552408913969	gnomAD-4.0.0	6.36568E-06	None	None	None	None	N	None	0	0	None	0	1.10939E-04	None	0	0	0	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
V/A	0.4544	ambiguous	0.5066	ambiguous	-1.634	Destabilizing	0.333	N	0.346	neutral	N	0.483265884	None	None	N
V/C	0.8554	likely_pathogenic	0.8703	pathogenic	-1.333	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
V/D	0.9832	likely_pathogenic	0.9809	pathogenic	-2.219	Highly Destabilizing	0.999	D	0.865	deleterious	None	None	None	None	N
V/E	0.9518	likely_pathogenic	0.9461	pathogenic	-1.951	Destabilizing	0.998	D	0.821	deleterious	D	0.530274495	None	None	N
V/F	0.5805	likely_pathogenic	0.5828	pathogenic	-0.944	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
V/G	0.8391	likely_pathogenic	0.8424	pathogenic	-2.209	Highly Destabilizing	0.989	D	0.808	deleterious	D	0.541630801	None	None	N
V/H	0.9707	likely_pathogenic	0.9683	pathogenic	-2.128	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
V/I	0.0899	likely_benign	0.091	benign	-0.02	Destabilizing	0.99	D	0.561	neutral	None	None	None	None	N
V/K	0.9461	likely_pathogenic	0.9367	pathogenic	-1.354	Destabilizing	0.999	D	0.832	deleterious	None	None	None	None	N
V/L	0.3494	ambiguous	0.3819	ambiguous	-0.02	Destabilizing	0.973	D	0.681	prob.neutral	D	0.522961902	None	None	N
V/M	0.3509	ambiguous	0.3756	ambiguous	-0.23	Destabilizing	0.999	D	0.703	prob.neutral	N	0.504915312	None	None	N
V/N	0.9428	likely_pathogenic	0.9427	pathogenic	-1.816	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
V/P	0.9759	likely_pathogenic	0.9737	pathogenic	-0.531	Destabilizing	0.999	D	0.842	deleterious	None	None	None	None	N
V/Q	0.932	likely_pathogenic	0.9263	pathogenic	-1.529	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
V/R	0.927	likely_pathogenic	0.9146	pathogenic	-1.485	Destabilizing	0.999	D	0.859	deleterious	None	None	None	None	N
V/S	0.7836	likely_pathogenic	0.8004	pathogenic	-2.43	Highly Destabilizing	0.983	D	0.787	deleterious	None	None	None	None	N
V/T	0.6958	likely_pathogenic	0.7229	pathogenic	-1.987	Destabilizing	0.992	D	0.685	prob.neutral	None	None	None	None	N
V/W	0.9862	likely_pathogenic	0.9846	pathogenic	-1.465	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
V/Y	0.9276	likely_pathogenic	0.9264	pathogenic	-1.001	Destabilizing	1.0	D	0.748	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.