TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20865	62818;62819;62820	chr2:178589132;178589131;178589130	chr2:179453859;179453858;179453857
N2AB	19224	57895;57896;57897	chr2:178589132;178589131;178589130	chr2:179453859;179453858;179453857
N2A	18297	55114;55115;55116	chr2:178589132;178589131;178589130	chr2:179453859;179453858;179453857
N2B	11800	35623;35624;35625	chr2:178589132;178589131;178589130	chr2:179453859;179453858;179453857
Novex-1	11925	35998;35999;36000	chr2:178589132;178589131;178589130	chr2:179453859;179453858;179453857
Novex-2	11992	36199;36200;36201	chr2:178589132;178589131;178589130	chr2:179453859;179453858;179453857
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-39
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.1101
• 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
P/T	rs757101265	-2.25	1.0	D	0.769	0.692	0.808403628478	gnomAD-2.1.1	2.82E-05	None	None	None	None	N	None	0	0	None	0	0	None	2.28803E-04	None	0	0	0
P/T	rs757101265	-2.25	1.0	D	0.769	0.692	0.808403628478	gnomAD-4.0.0	1.84847E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99556E-07	3.0147E-04	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
P/A	0.9357	likely_pathogenic	0.9407	pathogenic	-1.565	Destabilizing	0.999	D	0.816	deleterious	D	0.612162348	None	None	N
P/C	0.9962	likely_pathogenic	0.9967	pathogenic	-1.943	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
P/D	0.9994	likely_pathogenic	0.9995	pathogenic	-3.267	Highly Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
P/E	0.9987	likely_pathogenic	0.9989	pathogenic	-3.196	Highly Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
P/F	0.9998	likely_pathogenic	0.9998	pathogenic	-1.067	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
P/G	0.9955	likely_pathogenic	0.9956	pathogenic	-1.9	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
P/H	0.9988	likely_pathogenic	0.999	pathogenic	-1.345	Destabilizing	1.0	D	0.781	deleterious	D	0.654325233	None	None	N
P/I	0.9958	likely_pathogenic	0.9969	pathogenic	-0.695	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
P/K	0.999	likely_pathogenic	0.9993	pathogenic	-1.49	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
P/L	0.9874	likely_pathogenic	0.9903	pathogenic	-0.695	Destabilizing	1.0	D	0.816	deleterious	D	0.638104068	None	None	N
P/M	0.9981	likely_pathogenic	0.9985	pathogenic	-0.934	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
P/N	0.9994	likely_pathogenic	0.9995	pathogenic	-1.807	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
P/Q	0.9984	likely_pathogenic	0.9987	pathogenic	-1.942	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
P/R	0.9965	likely_pathogenic	0.9973	pathogenic	-1.043	Destabilizing	1.0	D	0.821	deleterious	D	0.654123429	None	None	N
P/S	0.9955	likely_pathogenic	0.9958	pathogenic	-2.136	Highly Destabilizing	1.0	D	0.764	deleterious	D	0.653921625	None	None	N
P/T	0.9918	likely_pathogenic	0.9926	pathogenic	-1.964	Destabilizing	1.0	D	0.769	deleterious	D	0.654123429	None	None	N
P/V	0.9861	likely_pathogenic	0.9888	pathogenic	-0.958	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
P/W	0.9999	likely_pathogenic	0.9999	pathogenic	-1.427	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
P/Y	0.9996	likely_pathogenic	0.9997	pathogenic	-1.101	Destabilizing	1.0	D	0.825	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.