TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24146	72661;72662;72663	chr2:178573696;178573695;178573694	chr2:179438423;179438422;179438421
N2AB	22505	67738;67739;67740	chr2:178573696;178573695;178573694	chr2:179438423;179438422;179438421
N2A	21578	64957;64958;64959	chr2:178573696;178573695;178573694	chr2:179438423;179438422;179438421
N2B	15081	45466;45467;45468	chr2:178573696;178573695;178573694	chr2:179438423;179438422;179438421
Novex-1	15206	45841;45842;45843	chr2:178573696;178573695;178573694	chr2:179438423;179438422;179438421
Novex-2	15273	46042;46043;46044	chr2:178573696;178573695;178573694	chr2:179438423;179438422;179438421
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: Fn3-63
• Domain position: 25
• Structural Position: 26
• Q(SASA): 0.4052
• 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/R	rs1184232674	-1.184	0.999	N	0.781	0.472	0.520586239559	gnomAD-2.1.1	5.49E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.49E-05	None	0	0	0
P/R	rs1184232674	-1.184	0.999	N	0.781	0.472	0.520586239559	gnomAD-4.0.0	1.8529E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.42489E-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	0.088	likely_benign	0.1008	benign	-1.826	Destabilizing	0.998	D	0.597	neutral	N	0.501264052	None	None	N
P/C	0.432	ambiguous	0.5135	ambiguous	-1.189	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
P/D	0.6282	likely_pathogenic	0.7001	pathogenic	-2.041	Highly Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
P/E	0.3372	likely_benign	0.3776	ambiguous	-1.905	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
P/F	0.512	ambiguous	0.5954	pathogenic	-1.189	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
P/G	0.4353	ambiguous	0.4983	ambiguous	-2.247	Highly Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
P/H	0.2052	likely_benign	0.2604	benign	-1.68	Destabilizing	0.434	N	0.448	neutral	N	0.500053466	None	None	N
P/I	0.2934	likely_benign	0.3499	ambiguous	-0.697	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
P/K	0.3259	likely_benign	0.3811	ambiguous	-1.572	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
P/L	0.1162	likely_benign	0.1373	benign	-0.697	Destabilizing	0.999	D	0.769	deleterious	N	0.502015249	None	None	N
P/M	0.3144	likely_benign	0.3663	ambiguous	-0.612	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
P/N	0.478	ambiguous	0.5562	ambiguous	-1.645	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
P/Q	0.1789	likely_benign	0.2062	benign	-1.643	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
P/R	0.2045	likely_benign	0.248	benign	-1.195	Destabilizing	0.999	D	0.781	deleterious	N	0.49978675	None	None	N
P/S	0.1457	likely_benign	0.1857	benign	-2.195	Highly Destabilizing	0.999	D	0.691	prob.neutral	N	0.499533261	None	None	N
P/T	0.1428	likely_benign	0.1809	benign	-1.93	Destabilizing	1.0	D	0.717	prob.delet.	N	0.511801392	None	None	N
P/V	0.2014	likely_benign	0.2397	benign	-1.045	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
P/W	0.6827	likely_pathogenic	0.7577	pathogenic	-1.503	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
P/Y	0.4813	ambiguous	0.5782	pathogenic	-1.16	Destabilizing	0.999	D	0.803	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.