TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31933	96022;96023;96024	chr2:178544432;178544431;178544430	chr2:179409159;179409158;179409157
N2AB	30292	91099;91100;91101	chr2:178544432;178544431;178544430	chr2:179409159;179409158;179409157
N2A	29365	88318;88319;88320	chr2:178544432;178544431;178544430	chr2:179409159;179409158;179409157
N2B	22868	68827;68828;68829	chr2:178544432;178544431;178544430	chr2:179409159;179409158;179409157
Novex-1	22993	69202;69203;69204	chr2:178544432;178544431;178544430	chr2:179409159;179409158;179409157
Novex-2	23060	69403;69404;69405	chr2:178544432;178544431;178544430	chr2:179409159;179409158;179409157
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-121
• Domain position: 25
• Structural Position: 27
• Q(SASA): 0.1875
• 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/A	None	None	1.0	D	0.831	0.552	0.656232129661	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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	0.7881	likely_pathogenic	0.7208	pathogenic	-1.898	Destabilizing	1.0	D	0.831	deleterious	D	0.593901753	None	None	N
P/C	0.9863	likely_pathogenic	0.9799	pathogenic	-1.358	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
P/D	0.997	likely_pathogenic	0.9951	pathogenic	-1.986	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
P/E	0.9932	likely_pathogenic	0.9893	pathogenic	-1.919	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
P/F	0.999	likely_pathogenic	0.9983	pathogenic	-1.343	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
P/G	0.9728	likely_pathogenic	0.9586	pathogenic	-2.304	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
P/H	0.9934	likely_pathogenic	0.9892	pathogenic	-1.92	Destabilizing	1.0	D	0.881	deleterious	D	0.636064639	None	None	N
P/I	0.9909	likely_pathogenic	0.986	pathogenic	-0.837	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/K	0.9972	likely_pathogenic	0.9956	pathogenic	-1.653	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
P/L	0.9629	likely_pathogenic	0.9361	pathogenic	-0.837	Destabilizing	1.0	D	0.905	deleterious	D	0.619036256	None	None	N
P/M	0.992	likely_pathogenic	0.9866	pathogenic	-0.66	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
P/N	0.9929	likely_pathogenic	0.9895	pathogenic	-1.541	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
P/Q	0.9891	likely_pathogenic	0.9821	pathogenic	-1.627	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
P/R	0.9927	likely_pathogenic	0.9881	pathogenic	-1.196	Destabilizing	1.0	D	0.9	deleterious	D	0.635862834	None	None	N
P/S	0.95	likely_pathogenic	0.9218	pathogenic	-2.113	Highly Destabilizing	1.0	D	0.855	deleterious	D	0.556119636	None	None	N
P/T	0.9481	likely_pathogenic	0.9186	pathogenic	-1.925	Destabilizing	1.0	D	0.85	deleterious	D	0.594103558	None	None	N
P/V	0.9674	likely_pathogenic	0.9506	pathogenic	-1.158	Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
P/W	0.9996	likely_pathogenic	0.9992	pathogenic	-1.639	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
P/Y	0.9985	likely_pathogenic	0.9975	pathogenic	-1.344	Destabilizing	1.0	D	0.899	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.