TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26583	79972;79973;79974	chr2:178566385;178566384;178566383	chr2:179431112;179431111;179431110
N2AB	24942	75049;75050;75051	chr2:178566385;178566384;178566383	chr2:179431112;179431111;179431110
N2A	24015	72268;72269;72270	chr2:178566385;178566384;178566383	chr2:179431112;179431111;179431110
N2B	17518	52777;52778;52779	chr2:178566385;178566384;178566383	chr2:179431112;179431111;179431110
Novex-1	17643	53152;53153;53154	chr2:178566385;178566384;178566383	chr2:179431112;179431111;179431110
Novex-2	17710	53353;53354;53355	chr2:178566385;178566384;178566383	chr2:179431112;179431111;179431110
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-81
• Domain position: 97
• Structural Position: 130
• Q(SASA): 0.0744
• 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/L	None	None	1.0	N	0.835	0.442	0.642006589361	gnomAD-4.0.0	6.84321E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9953E-07	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
P/A	0.1185	likely_benign	0.1178	benign	-2.576	Highly Destabilizing	0.999	D	0.819	deleterious	N	0.405284661	None	None	N
P/C	0.7724	likely_pathogenic	0.7679	pathogenic	-2.511	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
P/D	0.9964	likely_pathogenic	0.9967	pathogenic	-3.416	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
P/E	0.9813	likely_pathogenic	0.983	pathogenic	-3.193	Highly Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
P/F	0.9871	likely_pathogenic	0.9892	pathogenic	-1.182	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
P/G	0.8511	likely_pathogenic	0.8556	pathogenic	-3.008	Highly Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
P/H	0.9853	likely_pathogenic	0.9864	pathogenic	-2.416	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
P/I	0.639	likely_pathogenic	0.6212	pathogenic	-1.327	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
P/K	0.9888	likely_pathogenic	0.9898	pathogenic	-2.05	Highly Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
P/L	0.4984	ambiguous	0.4997	ambiguous	-1.327	Destabilizing	1.0	D	0.835	deleterious	N	0.501680631	None	None	N
P/M	0.7776	likely_pathogenic	0.8141	pathogenic	-1.79	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
P/N	0.9828	likely_pathogenic	0.9818	pathogenic	-2.575	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
P/Q	0.9588	likely_pathogenic	0.964	pathogenic	-2.346	Highly Destabilizing	1.0	D	0.834	deleterious	N	0.49271113	None	None	N
P/R	0.9687	likely_pathogenic	0.9694	pathogenic	-1.895	Destabilizing	1.0	D	0.853	deleterious	N	0.49271113	None	None	N
P/S	0.7345	likely_pathogenic	0.7381	pathogenic	-3.008	Highly Destabilizing	1.0	D	0.785	deleterious	N	0.491190193	None	None	N
P/T	0.46	ambiguous	0.4613	ambiguous	-2.671	Highly Destabilizing	1.0	D	0.797	deleterious	N	0.512030911	None	None	N
P/V	0.3735	ambiguous	0.3685	ambiguous	-1.729	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
P/W	0.9967	likely_pathogenic	0.9974	pathogenic	-1.586	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
P/Y	0.992	likely_pathogenic	0.9932	pathogenic	-1.499	Destabilizing	1.0	D	0.863	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.