TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9025	27298;27299;27300	chr2:178712952;178712951;178712950	chr2:179577679;179577678;179577677
N2AB	8708	26347;26348;26349	chr2:178712952;178712951;178712950	chr2:179577679;179577678;179577677
N2A	7781	23566;23567;23568	chr2:178712952;178712951;178712950	chr2:179577679;179577678;179577677
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-76
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.1987
• 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	rs1203714029	-0.572	0.121	N	0.486	0.218	0.454331543959	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.49E-05	0
P/L	rs1203714029	-0.572	0.121	N	0.486	0.218	0.454331543959	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/L	rs1203714029	-0.572	0.121	N	0.486	0.218	0.454331543959	gnomAD-4.0.0	6.41422E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.19807E-05	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	0.3652	ambiguous	0.4576	ambiguous	-1.784	Destabilizing	0.989	D	0.537	neutral	D	0.531050374	None	None	N
P/C	0.9464	likely_pathogenic	0.9611	pathogenic	-1.283	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
P/D	0.977	likely_pathogenic	0.9894	pathogenic	-2.088	Highly Destabilizing	0.999	D	0.666	neutral	None	None	None	None	N
P/E	0.9366	likely_pathogenic	0.9695	pathogenic	-1.939	Destabilizing	0.999	D	0.649	neutral	None	None	None	None	N
P/F	0.9646	likely_pathogenic	0.9776	pathogenic	-1.083	Destabilizing	0.995	D	0.757	deleterious	None	None	None	None	N
P/G	0.8739	likely_pathogenic	0.9188	pathogenic	-2.264	Highly Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
P/H	0.9309	likely_pathogenic	0.9624	pathogenic	-2.013	Highly Destabilizing	1.0	D	0.686	prob.neutral	D	0.532317822	None	None	N
P/I	0.7737	likely_pathogenic	0.824	pathogenic	-0.481	Destabilizing	0.643	D	0.471	neutral	None	None	None	None	N
P/K	0.9677	likely_pathogenic	0.9834	pathogenic	-1.313	Destabilizing	0.999	D	0.644	neutral	None	None	None	None	N
P/L	0.4747	ambiguous	0.5402	ambiguous	-0.481	Destabilizing	0.121	N	0.486	neutral	N	0.492598922	None	None	N
P/M	0.7694	likely_pathogenic	0.8127	pathogenic	-0.475	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
P/N	0.9648	likely_pathogenic	0.9809	pathogenic	-1.412	Destabilizing	0.999	D	0.688	prob.neutral	None	None	None	None	N
P/Q	0.887	likely_pathogenic	0.9361	pathogenic	-1.363	Destabilizing	0.999	D	0.666	neutral	None	None	None	None	N
P/R	0.9317	likely_pathogenic	0.9664	pathogenic	-1.113	Destabilizing	0.999	D	0.684	prob.neutral	D	0.531810843	None	None	N
P/S	0.798	likely_pathogenic	0.8822	pathogenic	-2.033	Highly Destabilizing	0.999	D	0.653	neutral	N	0.490740487	None	None	N
P/T	0.5855	likely_pathogenic	0.7056	pathogenic	-1.752	Destabilizing	0.997	D	0.654	neutral	N	0.513453098	None	None	N
P/V	0.662	likely_pathogenic	0.7292	pathogenic	-0.886	Destabilizing	0.967	D	0.533	neutral	None	None	None	None	N
P/W	0.9873	likely_pathogenic	0.9933	pathogenic	-1.531	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
P/Y	0.9782	likely_pathogenic	0.9893	pathogenic	-1.157	Destabilizing	0.999	D	0.756	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.