TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3841	11746;11747;11748	chr2:178741712;178741711;178741710	chr2:179606439;179606438;179606437
N2AB	3524	10795;10796;10797	chr2:178741712;178741711;178741710	chr2:179606439;179606438;179606437
N2A	None	None	chr2:None	chr2:None
N2B	3478	10657;10658;10659	chr2:178741712;178741711;178741710	chr2:179606439;179606438;179606437
Novex-1	3603	11032;11033;11034	chr2:178741712;178741711;178741710	chr2:179606439;179606438;179606437
Novex-2	3670	11233;11234;11235	chr2:178741712;178741711;178741710	chr2:179606439;179606438;179606437
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-27
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.0774
• 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
V/I	rs755132807	-0.178	0.997	N	0.588	0.339	None	gnomAD-2.1.1	2.14E-05	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	3.91E-05	0
V/I	rs755132807	-0.178	0.997	N	0.588	0.339	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
V/I	rs755132807	-0.178	0.997	N	0.588	0.339	None	gnomAD-4.0.0	2.35496E-05	None	None	None	None	N	None	1.33501E-05	0	None	0	0	None	0	1.64366E-04	2.20387E-05	8.78291E-05	3.20266E-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
V/A	0.476	ambiguous	0.4066	ambiguous	-2.238	Highly Destabilizing	0.999	D	0.715	prob.delet.	N	0.451946431	None	None	N
V/C	0.9038	likely_pathogenic	0.8935	pathogenic	-2.048	Highly Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
V/D	0.9823	likely_pathogenic	0.9794	pathogenic	-3.243	Highly Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	N
V/E	0.9612	likely_pathogenic	0.9589	pathogenic	-2.981	Highly Destabilizing	1.0	D	0.914	deleterious	D	0.574409822	None	None	N
V/F	0.7405	likely_pathogenic	0.6879	pathogenic	-1.216	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
V/G	0.7252	likely_pathogenic	0.674	pathogenic	-2.81	Highly Destabilizing	1.0	D	0.908	deleterious	N	0.449765476	None	None	N
V/H	0.9914	likely_pathogenic	0.9899	pathogenic	-2.652	Highly Destabilizing	1.0	D	0.935	deleterious	None	None	None	None	N
V/I	0.1339	likely_benign	0.1231	benign	-0.605	Destabilizing	0.997	D	0.588	neutral	N	0.443448408	None	None	N
V/K	0.9734	likely_pathogenic	0.9745	pathogenic	-1.836	Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
V/L	0.6351	likely_pathogenic	0.5818	pathogenic	-0.605	Destabilizing	0.997	D	0.707	prob.neutral	N	0.442190736	None	None	N
V/M	0.4831	ambiguous	0.4142	ambiguous	-0.908	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
V/N	0.9505	likely_pathogenic	0.936	pathogenic	-2.346	Highly Destabilizing	1.0	D	0.939	deleterious	None	None	None	None	N
V/P	0.9912	likely_pathogenic	0.9894	pathogenic	-1.127	Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
V/Q	0.9648	likely_pathogenic	0.9622	pathogenic	-2.1	Highly Destabilizing	1.0	D	0.943	deleterious	None	None	None	None	N
V/R	0.9583	likely_pathogenic	0.9631	pathogenic	-1.778	Destabilizing	1.0	D	0.944	deleterious	None	None	None	None	N
V/S	0.7714	likely_pathogenic	0.7092	pathogenic	-2.912	Highly Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
V/T	0.5986	likely_pathogenic	0.5277	ambiguous	-2.503	Highly Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
V/W	0.997	likely_pathogenic	0.9961	pathogenic	-1.829	Destabilizing	1.0	D	0.939	deleterious	None	None	None	None	N
V/Y	0.9779	likely_pathogenic	0.9752	pathogenic	-1.493	Destabilizing	1.0	D	0.867	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.