TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21833	65722;65723;65724	chr2:178583685;178583684;178583683	chr2:179448412;179448411;179448410
N2AB	20192	60799;60800;60801	chr2:178583685;178583684;178583683	chr2:179448412;179448411;179448410
N2A	19265	58018;58019;58020	chr2:178583685;178583684;178583683	chr2:179448412;179448411;179448410
N2B	12768	38527;38528;38529	chr2:178583685;178583684;178583683	chr2:179448412;179448411;179448410
Novex-1	12893	38902;38903;38904	chr2:178583685;178583684;178583683	chr2:179448412;179448411;179448410
Novex-2	12960	39103;39104;39105	chr2:178583685;178583684;178583683	chr2:179448412;179448411;179448410
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-46
• Domain position: 77
• Structural Position: 107
• Q(SASA): 0.1381
• 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
R/T	None	None	0.967	N	0.625	0.405	0.674717478158	gnomAD-4.0.0	1.59485E-06	None	None	None	None	N	None	0	0	None	0	2.79392E-05	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
R/A	0.9895	likely_pathogenic	0.9898	pathogenic	-1.894	Destabilizing	0.845	D	0.638	neutral	None	None	None	None	N
R/C	0.6847	likely_pathogenic	0.6956	pathogenic	-1.811	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
R/D	0.9988	likely_pathogenic	0.9988	pathogenic	-0.825	Destabilizing	0.975	D	0.691	prob.neutral	None	None	None	None	N
R/E	0.9802	likely_pathogenic	0.98	pathogenic	-0.605	Destabilizing	0.845	D	0.642	neutral	None	None	None	None	N
R/F	0.9874	likely_pathogenic	0.9879	pathogenic	-1.105	Destabilizing	0.996	D	0.806	deleterious	None	None	None	None	N
R/G	0.9892	likely_pathogenic	0.9873	pathogenic	-2.256	Highly Destabilizing	0.892	D	0.669	neutral	D	0.543121604	None	None	N
R/H	0.423	ambiguous	0.4413	ambiguous	-2.027	Highly Destabilizing	0.987	D	0.637	neutral	None	None	None	None	N
R/I	0.9707	likely_pathogenic	0.9714	pathogenic	-0.846	Destabilizing	0.983	D	0.809	deleterious	N	0.506913094	None	None	N
R/K	0.6684	likely_pathogenic	0.6083	pathogenic	-1.261	Destabilizing	0.63	D	0.656	neutral	N	0.494743413	None	None	N
R/L	0.9391	likely_pathogenic	0.9418	pathogenic	-0.846	Destabilizing	0.916	D	0.669	neutral	None	None	None	None	N
R/M	0.9785	likely_pathogenic	0.9774	pathogenic	-1.349	Destabilizing	0.997	D	0.687	prob.neutral	None	None	None	None	N
R/N	0.9937	likely_pathogenic	0.9942	pathogenic	-1.244	Destabilizing	0.975	D	0.586	neutral	None	None	None	None	N
R/P	0.9993	likely_pathogenic	0.9993	pathogenic	-1.183	Destabilizing	0.987	D	0.753	deleterious	None	None	None	None	N
R/Q	0.5641	likely_pathogenic	0.5594	ambiguous	-1.134	Destabilizing	0.253	N	0.429	neutral	None	None	None	None	N
R/S	0.9911	likely_pathogenic	0.9918	pathogenic	-2.177	Highly Destabilizing	0.805	D	0.619	neutral	N	0.516949045	None	None	N
R/T	0.9859	likely_pathogenic	0.987	pathogenic	-1.737	Destabilizing	0.967	D	0.625	neutral	N	0.492198972	None	None	N
R/V	0.9727	likely_pathogenic	0.9744	pathogenic	-1.183	Destabilizing	0.975	D	0.762	deleterious	None	None	None	None	N
R/W	0.801	likely_pathogenic	0.8421	pathogenic	-0.587	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
R/Y	0.9538	likely_pathogenic	0.961	pathogenic	-0.443	Destabilizing	0.987	D	0.782	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.