TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21370	64333;64334;64335	chr2:178586793;178586792;178586791	chr2:179451520;179451519;179451518
N2AB	19729	59410;59411;59412	chr2:178586793;178586792;178586791	chr2:179451520;179451519;179451518
N2A	18802	56629;56630;56631	chr2:178586793;178586792;178586791	chr2:179451520;179451519;179451518
N2B	12305	37138;37139;37140	chr2:178586793;178586792;178586791	chr2:179451520;179451519;179451518
Novex-1	12430	37513;37514;37515	chr2:178586793;178586792;178586791	chr2:179451520;179451519;179451518
Novex-2	12497	37714;37715;37716	chr2:178586793;178586792;178586791	chr2:179451520;179451519;179451518
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: Fn3-43
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.0827
• 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	rs2049075418	None	1.0	D	0.923	0.551	0.861509126281	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
P/L	rs2049075418	None	1.0	D	0.923	0.551	0.861509126281	gnomAD-4.0.0	1.86122E-06	None	None	None	None	N	None	1.33786E-05	0	None	0	0	None	0	0	1.6963E-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
P/A	0.9405	likely_pathogenic	0.8986	pathogenic	-2.486	Highly Destabilizing	1.0	D	0.843	deleterious	D	0.52538183	None	None	N
P/C	0.9841	likely_pathogenic	0.9822	pathogenic	-2.198	Highly Destabilizing	1.0	D	0.923	deleterious	None	None	None	None	N
P/D	0.9998	likely_pathogenic	0.9997	pathogenic	-3.337	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
P/E	0.9995	likely_pathogenic	0.999	pathogenic	-3.08	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
P/F	0.9998	likely_pathogenic	0.9995	pathogenic	-1.082	Destabilizing	1.0	D	0.939	deleterious	None	None	None	None	N
P/G	0.9982	likely_pathogenic	0.9972	pathogenic	-2.989	Highly Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
P/H	0.9996	likely_pathogenic	0.9993	pathogenic	-2.581	Highly Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
P/I	0.9405	likely_pathogenic	0.8958	pathogenic	-1.027	Destabilizing	1.0	D	0.944	deleterious	None	None	None	None	N
P/K	0.9997	likely_pathogenic	0.9994	pathogenic	-1.926	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
P/L	0.9654	likely_pathogenic	0.9324	pathogenic	-1.027	Destabilizing	1.0	D	0.923	deleterious	D	0.551119407	None	None	N
P/M	0.9959	likely_pathogenic	0.9921	pathogenic	-1.472	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
P/N	0.9997	likely_pathogenic	0.9994	pathogenic	-2.454	Highly Destabilizing	1.0	D	0.945	deleterious	None	None	None	None	N
P/Q	0.9991	likely_pathogenic	0.9983	pathogenic	-2.172	Highly Destabilizing	1.0	D	0.906	deleterious	D	0.541372944	None	None	N
P/R	0.9989	likely_pathogenic	0.9982	pathogenic	-1.852	Destabilizing	1.0	D	0.946	deleterious	D	0.56374316	None	None	N
P/S	0.996	likely_pathogenic	0.9931	pathogenic	-2.94	Highly Destabilizing	1.0	D	0.886	deleterious	D	0.545892395	None	None	N
P/T	0.9865	likely_pathogenic	0.9765	pathogenic	-2.559	Highly Destabilizing	1.0	D	0.881	deleterious	D	0.529002681	None	None	N
P/V	0.809	likely_pathogenic	0.7307	pathogenic	-1.497	Destabilizing	1.0	D	0.923	deleterious	None	None	None	None	N
P/W	1.0	likely_pathogenic	0.9999	pathogenic	-1.606	Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
P/Y	0.9999	likely_pathogenic	0.9998	pathogenic	-1.436	Destabilizing	1.0	D	0.945	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.