TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22750	68473;68474;68475	chr2:178578692;178578691;178578690	chr2:179443419;179443418;179443417
N2AB	21109	63550;63551;63552	chr2:178578692;178578691;178578690	chr2:179443419;179443418;179443417
N2A	20182	60769;60770;60771	chr2:178578692;178578691;178578690	chr2:179443419;179443418;179443417
N2B	13685	41278;41279;41280	chr2:178578692;178578691;178578690	chr2:179443419;179443418;179443417
Novex-1	13810	41653;41654;41655	chr2:178578692;178578691;178578690	chr2:179443419;179443418;179443417
Novex-2	13877	41854;41855;41856	chr2:178578692;178578691;178578690	chr2:179443419;179443418;179443417
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: Fn3-53
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.2148
• 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	rs764562311	-1.583	0.957	D	0.492	0.46	0.400033932507	gnomAD-2.1.1	1.22E-05	None	None	None	None	N	None	0	2.93E-05	None	9.99E-05	0	None	0	None	0	0	1.67842E-04
P/S	rs764562311	-1.583	0.957	D	0.492	0.46	0.400033932507	gnomAD-4.0.0	6.85264E-06	None	None	None	None	N	None	2.99904E-05	4.49721E-05	None	7.66401E-05	0	None	0	0	2.70024E-06	0	3.3195E-05

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	0.5192	ambiguous	0.471	ambiguous	-2.172	Highly Destabilizing	0.992	D	0.728	prob.delet.	N	0.51918709	None	None	N
P/C	0.8642	likely_pathogenic	0.8467	pathogenic	-2.172	Highly Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
P/D	0.9986	likely_pathogenic	0.9986	pathogenic	-2.716	Highly Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
P/E	0.9934	likely_pathogenic	0.9942	pathogenic	-2.499	Highly Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
P/F	0.9925	likely_pathogenic	0.9919	pathogenic	-1.303	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
P/G	0.97	likely_pathogenic	0.9663	pathogenic	-2.704	Highly Destabilizing	0.997	D	0.787	deleterious	None	None	None	None	N
P/H	0.9919	likely_pathogenic	0.9914	pathogenic	-2.352	Highly Destabilizing	1.0	D	0.839	deleterious	D	0.549661608	None	None	N
P/I	0.7017	likely_pathogenic	0.6975	pathogenic	-0.688	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
P/K	0.9953	likely_pathogenic	0.9959	pathogenic	-1.722	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
P/L	0.5314	ambiguous	0.4988	ambiguous	-0.688	Destabilizing	0.999	D	0.852	deleterious	N	0.464984504	None	None	N
P/M	0.8799	likely_pathogenic	0.8737	pathogenic	-1.075	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
P/N	0.9958	likely_pathogenic	0.9956	pathogenic	-2.077	Highly Destabilizing	0.999	D	0.846	deleterious	None	None	None	None	N
P/Q	0.9828	likely_pathogenic	0.9826	pathogenic	-1.934	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
P/R	0.988	likely_pathogenic	0.9888	pathogenic	-1.584	Destabilizing	0.999	D	0.845	deleterious	D	0.549661608	None	None	N
P/S	0.9483	likely_pathogenic	0.9384	pathogenic	-2.74	Highly Destabilizing	0.957	D	0.492	neutral	D	0.538051813	None	None	N
P/T	0.8209	likely_pathogenic	0.8067	pathogenic	-2.37	Highly Destabilizing	0.998	D	0.825	deleterious	D	0.549154629	None	None	N
P/V	0.4838	ambiguous	0.4556	ambiguous	-1.156	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
P/W	0.9988	likely_pathogenic	0.9987	pathogenic	-1.712	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
P/Y	0.9973	likely_pathogenic	0.9974	pathogenic	-1.369	Destabilizing	1.0	D	0.881	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.