TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16560	49903;49904;49905	chr2:178613043;178613042;178613041	chr2:179477770;179477769;179477768
N2AB	14919	44980;44981;44982	chr2:178613043;178613042;178613041	chr2:179477770;179477769;179477768
N2A	13992	42199;42200;42201	chr2:178613043;178613042;178613041	chr2:179477770;179477769;179477768
N2B	7495	22708;22709;22710	chr2:178613043;178613042;178613041	chr2:179477770;179477769;179477768
Novex-1	7620	23083;23084;23085	chr2:178613043;178613042;178613041	chr2:179477770;179477769;179477768
Novex-2	7687	23284;23285;23286	chr2:178613043;178613042;178613041	chr2:179477770;179477769;179477768
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-8
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.3669
• 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/I	rs966629788	-0.418	0.767	N	0.286	0.178	0.438064232554	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
V/I	rs966629788	-0.418	0.767	N	0.286	0.178	0.438064232554	gnomAD-4.0.0	9.5616E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	8.60141E-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
V/A	0.4647	ambiguous	0.5125	ambiguous	-1.508	Destabilizing	0.998	D	0.58	neutral	N	0.48397852	None	None	N
V/C	0.8853	likely_pathogenic	0.8709	pathogenic	-1.17	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
V/D	0.9499	likely_pathogenic	0.9742	pathogenic	-1.125	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/E	0.8729	likely_pathogenic	0.9259	pathogenic	-1.082	Destabilizing	1.0	D	0.861	deleterious	D	0.654247609	None	None	N
V/F	0.494	ambiguous	0.5206	ambiguous	-1.053	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
V/G	0.675	likely_pathogenic	0.7593	pathogenic	-1.872	Destabilizing	1.0	D	0.853	deleterious	D	0.652414251	None	None	N
V/H	0.9608	likely_pathogenic	0.9714	pathogenic	-1.333	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/I	0.0881	likely_benign	0.0787	benign	-0.595	Destabilizing	0.767	D	0.286	neutral	N	0.487074979	None	None	N
V/K	0.9119	likely_pathogenic	0.9475	pathogenic	-1.326	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
V/L	0.3485	ambiguous	0.3441	ambiguous	-0.595	Destabilizing	0.981	D	0.466	neutral	N	0.478329985	None	None	N
V/M	0.3485	ambiguous	0.3604	ambiguous	-0.548	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
V/N	0.8876	likely_pathogenic	0.9148	pathogenic	-1.208	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
V/P	0.7043	likely_pathogenic	0.7213	pathogenic	-0.864	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/Q	0.8726	likely_pathogenic	0.9115	pathogenic	-1.279	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
V/R	0.8749	likely_pathogenic	0.9265	pathogenic	-0.882	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
V/S	0.7241	likely_pathogenic	0.7842	pathogenic	-1.802	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
V/T	0.5646	likely_pathogenic	0.6231	pathogenic	-1.626	Destabilizing	0.998	D	0.713	prob.delet.	None	None	None	None	N
V/W	0.9657	likely_pathogenic	0.9732	pathogenic	-1.256	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
V/Y	0.9075	likely_pathogenic	0.9208	pathogenic	-0.955	Destabilizing	1.0	D	0.881	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.