TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2873	8842;8843;8844	chr2:178770084;178770083;178770082	chr2:179634811;179634810;179634809
N2AB	2873	8842;8843;8844	chr2:178770084;178770083;178770082	chr2:179634811;179634810;179634809
N2A	2873	8842;8843;8844	chr2:178770084;178770083;178770082	chr2:179634811;179634810;179634809
N2B	2827	8704;8705;8706	chr2:178770084;178770083;178770082	chr2:179634811;179634810;179634809
Novex-1	2827	8704;8705;8706	chr2:178770084;178770083;178770082	chr2:179634811;179634810;179634809
Novex-2	2827	8704;8705;8706	chr2:178770084;178770083;178770082	chr2:179634811;179634810;179634809
Novex-3	2873	8842;8843;8844	chr2:178770084;178770083;178770082	chr2:179634811;179634810;179634809

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-18
• Domain position: 79
• Structural Position: 169
• Q(SASA): 0.1384
• 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
C/G	None	None	0.669	D	0.741	0.432	0.809333530915	gnomAD-4.0.0	2.05218E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69787E-06	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
C/A	0.6668	likely_pathogenic	0.7361	pathogenic	-1.921	Destabilizing	0.525	D	0.525	neutral	None	None	None	None	N
C/D	0.9774	likely_pathogenic	0.9868	pathogenic	-0.671	Destabilizing	0.949	D	0.799	deleterious	None	None	None	None	N
C/E	0.9873	likely_pathogenic	0.9909	pathogenic	-0.543	Destabilizing	0.949	D	0.801	deleterious	None	None	None	None	N
C/F	0.7037	likely_pathogenic	0.7839	pathogenic	-1.123	Destabilizing	0.989	D	0.799	deleterious	D	0.564733331	None	None	N
C/G	0.4829	ambiguous	0.6247	pathogenic	-2.255	Highly Destabilizing	0.669	D	0.741	deleterious	D	0.564733331	None	None	N
C/H	0.9603	likely_pathogenic	0.9757	pathogenic	-2.14	Highly Destabilizing	0.998	D	0.793	deleterious	None	None	None	None	N
C/I	0.8444	likely_pathogenic	0.8848	pathogenic	-1.045	Destabilizing	0.949	D	0.772	deleterious	None	None	None	None	N
C/K	0.9946	likely_pathogenic	0.9962	pathogenic	-1.32	Destabilizing	0.949	D	0.798	deleterious	None	None	None	None	N
C/L	0.8463	likely_pathogenic	0.8815	pathogenic	-1.045	Destabilizing	0.842	D	0.678	prob.neutral	None	None	None	None	N
C/M	0.8512	likely_pathogenic	0.8701	pathogenic	0.054	Stabilizing	0.998	D	0.755	deleterious	None	None	None	None	N
C/N	0.9215	likely_pathogenic	0.951	pathogenic	-1.366	Destabilizing	0.949	D	0.8	deleterious	None	None	None	None	N
C/P	0.999	likely_pathogenic	0.9993	pathogenic	-1.312	Destabilizing	0.974	D	0.815	deleterious	None	None	None	None	N
C/Q	0.9694	likely_pathogenic	0.9794	pathogenic	-1.215	Destabilizing	0.974	D	0.831	deleterious	None	None	None	None	N
C/R	0.9695	likely_pathogenic	0.9791	pathogenic	-1.16	Destabilizing	0.934	D	0.823	deleterious	N	0.509067921	None	None	N
C/S	0.5748	likely_pathogenic	0.7075	pathogenic	-1.924	Destabilizing	0.051	N	0.473	neutral	N	0.459781244	None	None	N
C/T	0.6359	likely_pathogenic	0.7039	pathogenic	-1.61	Destabilizing	0.067	N	0.419	neutral	None	None	None	None	N
C/V	0.6855	likely_pathogenic	0.7354	pathogenic	-1.312	Destabilizing	0.842	D	0.688	prob.neutral	None	None	None	None	N
C/W	0.9366	likely_pathogenic	0.9593	pathogenic	-1.124	Destabilizing	0.997	D	0.767	deleterious	D	0.607828278	None	None	N
C/Y	0.8547	likely_pathogenic	0.9085	pathogenic	-1.149	Destabilizing	0.989	D	0.787	deleterious	D	0.541225595	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.