TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32403	97432;97433;97434	chr2:178542549;178542548;178542547	chr2:179407276;179407275;179407274
N2AB	30762	92509;92510;92511	chr2:178542549;178542548;178542547	chr2:179407276;179407275;179407274
N2A	29835	89728;89729;89730	chr2:178542549;178542548;178542547	chr2:179407276;179407275;179407274
N2B	23338	70237;70238;70239	chr2:178542549;178542548;178542547	chr2:179407276;179407275;179407274
Novex-1	23463	70612;70613;70614	chr2:178542549;178542548;178542547	chr2:179407276;179407275;179407274
Novex-2	23530	70813;70814;70815	chr2:178542549;178542548;178542547	chr2:179407276;179407275;179407274
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: Fn3-124
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.0853
• 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/S	None	None	1.0	D	0.83	0.76	0.65196615958	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	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
P/A	0.6225	likely_pathogenic	0.5252	ambiguous	-2.103	Highly Destabilizing	1.0	D	0.754	deleterious	D	0.548713097	None	None	N
P/C	0.9065	likely_pathogenic	0.8677	pathogenic	-1.887	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
P/D	0.9992	likely_pathogenic	0.9989	pathogenic	-3.273	Highly Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
P/E	0.9964	likely_pathogenic	0.9945	pathogenic	-3.034	Highly Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
P/F	0.9975	likely_pathogenic	0.9959	pathogenic	-1.092	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
P/G	0.9892	likely_pathogenic	0.9821	pathogenic	-2.631	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
P/H	0.9966	likely_pathogenic	0.9943	pathogenic	-2.501	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
P/I	0.7537	likely_pathogenic	0.6705	pathogenic	-0.608	Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
P/K	0.9979	likely_pathogenic	0.9967	pathogenic	-1.774	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
P/L	0.8058	likely_pathogenic	0.7176	pathogenic	-0.608	Destabilizing	1.0	D	0.889	deleterious	D	0.575211143	None	None	N
P/M	0.9548	likely_pathogenic	0.9266	pathogenic	-0.941	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
P/N	0.9976	likely_pathogenic	0.9962	pathogenic	-2.238	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
P/Q	0.992	likely_pathogenic	0.9865	pathogenic	-2.024	Highly Destabilizing	1.0	D	0.853	deleterious	D	0.575971612	None	None	N
P/R	0.9937	likely_pathogenic	0.99	pathogenic	-1.684	Destabilizing	1.0	D	0.909	deleterious	D	0.575971612	None	None	N
P/S	0.9634	likely_pathogenic	0.9389	pathogenic	-2.73	Highly Destabilizing	1.0	D	0.83	deleterious	D	0.564361817	None	None	N
P/T	0.8863	likely_pathogenic	0.8251	pathogenic	-2.359	Highly Destabilizing	1.0	D	0.821	deleterious	D	0.553005511	None	None	N
P/V	0.5154	ambiguous	0.4114	ambiguous	-1.083	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
P/W	0.9997	likely_pathogenic	0.9995	pathogenic	-1.727	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
P/Y	0.9991	likely_pathogenic	0.9984	pathogenic	-1.368	Destabilizing	1.0	D	0.913	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.