TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20375	61348;61349;61350	chr2:178590602;178590601;178590600	chr2:179455329;179455328;179455327
N2AB	18734	56425;56426;56427	chr2:178590602;178590601;178590600	chr2:179455329;179455328;179455327
N2A	17807	53644;53645;53646	chr2:178590602;178590601;178590600	chr2:179455329;179455328;179455327
N2B	11310	34153;34154;34155	chr2:178590602;178590601;178590600	chr2:179455329;179455328;179455327
Novex-1	11435	34528;34529;34530	chr2:178590602;178590601;178590600	chr2:179455329;179455328;179455327
Novex-2	11502	34729;34730;34731	chr2:178590602;178590601;178590600	chr2:179455329;179455328;179455327
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-36
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.0906
• 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	rs1576090518	None	1.0	N	0.831	0.526	0.600586691565	gnomAD-4.0.0	4.78043E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.30812E-05	0
P/L	None	None	1.0	D	0.923	0.564	0.632073011451	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.9063	likely_pathogenic	0.8474	pathogenic	-2.533	Highly Destabilizing	1.0	D	0.831	deleterious	N	0.519581705	None	None	N
P/C	0.9836	likely_pathogenic	0.9651	pathogenic	-2.108	Highly Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
P/D	0.9997	likely_pathogenic	0.9995	pathogenic	-3.42	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
P/E	0.9993	likely_pathogenic	0.9987	pathogenic	-3.159	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
P/F	0.9996	likely_pathogenic	0.9993	pathogenic	-1.284	Destabilizing	1.0	D	0.931	deleterious	None	None	None	None	N
P/G	0.9953	likely_pathogenic	0.9926	pathogenic	-3.061	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
P/H	0.9989	likely_pathogenic	0.9981	pathogenic	-2.755	Highly Destabilizing	1.0	D	0.9	deleterious	D	0.563881291	None	None	N
P/I	0.9792	likely_pathogenic	0.9687	pathogenic	-1.008	Destabilizing	1.0	D	0.939	deleterious	None	None	None	None	N
P/K	0.9996	likely_pathogenic	0.9993	pathogenic	-2.099	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
P/L	0.9706	likely_pathogenic	0.9529	pathogenic	-1.008	Destabilizing	1.0	D	0.923	deleterious	D	0.551511028	None	None	N
P/M	0.9951	likely_pathogenic	0.9914	pathogenic	-1.321	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
P/N	0.9994	likely_pathogenic	0.999	pathogenic	-2.576	Highly Destabilizing	1.0	D	0.939	deleterious	None	None	None	None	N
P/Q	0.9986	likely_pathogenic	0.9973	pathogenic	-2.324	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
P/R	0.9984	likely_pathogenic	0.9972	pathogenic	-1.967	Destabilizing	1.0	D	0.939	deleterious	D	0.563627802	None	None	N
P/S	0.9926	likely_pathogenic	0.9862	pathogenic	-3.093	Highly Destabilizing	1.0	D	0.876	deleterious	D	0.552018007	None	None	N
P/T	0.9785	likely_pathogenic	0.9637	pathogenic	-2.705	Highly Destabilizing	1.0	D	0.871	deleterious	D	0.563374312	None	None	N
P/V	0.92	likely_pathogenic	0.8827	pathogenic	-1.498	Destabilizing	1.0	D	0.918	deleterious	None	None	None	None	N
P/W	0.9999	likely_pathogenic	0.9998	pathogenic	-1.849	Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
P/Y	0.9998	likely_pathogenic	0.9996	pathogenic	-1.602	Destabilizing	1.0	D	0.936	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.