TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21668	65227;65228;65229	chr2:178584549;178584548;178584547	chr2:179449276;179449275;179449274
N2AB	20027	60304;60305;60306	chr2:178584549;178584548;178584547	chr2:179449276;179449275;179449274
N2A	19100	57523;57524;57525	chr2:178584549;178584548;178584547	chr2:179449276;179449275;179449274
N2B	12603	38032;38033;38034	chr2:178584549;178584548;178584547	chr2:179449276;179449275;179449274
Novex-1	12728	38407;38408;38409	chr2:178584549;178584548;178584547	chr2:179449276;179449275;179449274
Novex-2	12795	38608;38609;38610	chr2:178584549;178584548;178584547	chr2:179449276;179449275;179449274
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: Fn3-45
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.2616
• 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/L	None	None	0.437	N	0.396	0.201	0.342400092842	gnomAD-4.0.0	1.59437E-06	None	None	None	None	N	None	0	0	None	0	2.78645E-05	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	0.5498	ambiguous	0.5133	ambiguous	-1.483	Destabilizing	0.78	D	0.537	neutral	N	0.505379006	None	None	N
V/C	0.8603	likely_pathogenic	0.8504	pathogenic	-1.151	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
V/D	0.9536	likely_pathogenic	0.9407	pathogenic	-1.259	Destabilizing	0.995	D	0.855	deleterious	N	0.498812472	None	None	N
V/E	0.8921	likely_pathogenic	0.87	pathogenic	-1.201	Destabilizing	0.996	D	0.828	deleterious	None	None	None	None	N
V/F	0.6164	likely_pathogenic	0.5221	ambiguous	-0.986	Destabilizing	0.968	D	0.757	deleterious	N	0.484779459	None	None	N
V/G	0.7421	likely_pathogenic	0.7152	pathogenic	-1.859	Destabilizing	0.995	D	0.83	deleterious	N	0.520511125	None	None	N
V/H	0.964	likely_pathogenic	0.9547	pathogenic	-1.324	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
V/I	0.0847	likely_benign	0.0818	benign	-0.532	Destabilizing	0.011	N	0.183	neutral	N	0.434655058	None	None	N
V/K	0.9123	likely_pathogenic	0.9066	pathogenic	-1.344	Destabilizing	0.988	D	0.829	deleterious	None	None	None	None	N
V/L	0.4509	ambiguous	0.397	ambiguous	-0.532	Destabilizing	0.437	N	0.396	neutral	N	0.519407095	None	None	N
V/M	0.44	ambiguous	0.3876	ambiguous	-0.514	Destabilizing	0.976	D	0.617	neutral	None	None	None	None	N
V/N	0.8747	likely_pathogenic	0.8516	pathogenic	-1.278	Destabilizing	0.996	D	0.848	deleterious	None	None	None	None	N
V/P	0.61	likely_pathogenic	0.6156	pathogenic	-0.814	Destabilizing	0.996	D	0.831	deleterious	None	None	None	None	N
V/Q	0.8848	likely_pathogenic	0.8703	pathogenic	-1.333	Destabilizing	0.996	D	0.822	deleterious	None	None	None	None	N
V/R	0.8894	likely_pathogenic	0.8764	pathogenic	-0.907	Destabilizing	0.996	D	0.853	deleterious	None	None	None	None	N
V/S	0.7898	likely_pathogenic	0.7572	pathogenic	-1.853	Destabilizing	0.988	D	0.779	deleterious	None	None	None	None	N
V/T	0.6394	likely_pathogenic	0.6115	pathogenic	-1.663	Destabilizing	0.919	D	0.605	neutral	None	None	None	None	N
V/W	0.9745	likely_pathogenic	0.9608	pathogenic	-1.223	Destabilizing	0.999	D	0.79	deleterious	None	None	None	None	N
V/Y	0.9196	likely_pathogenic	0.8868	pathogenic	-0.906	Destabilizing	0.996	D	0.768	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.