TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5897	17914;17915;17916	chr2:178730976;178730975;178730974	chr2:179595703;179595702;179595701
N2AB	5580	16963;16964;16965	chr2:178730976;178730975;178730974	chr2:179595703;179595702;179595701
N2A	4653	14182;14183;14184	chr2:178730976;178730975;178730974	chr2:179595703;179595702;179595701
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: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-42
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.0925
• 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/L	rs2080377213	None	0.997	N	0.626	0.469	0.622146358133	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07555E-04	0
V/L	rs2080377213	None	0.997	N	0.626	0.469	0.622146358133	gnomAD-4.0.0	6.57938E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.07555E-04	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
V/A	0.7379	likely_pathogenic	0.7202	pathogenic	-2.407	Highly Destabilizing	0.999	D	0.598	neutral	N	0.412626347	None	None	N
V/C	0.9669	likely_pathogenic	0.9644	pathogenic	-2.15	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
V/D	0.9959	likely_pathogenic	0.9966	pathogenic	-3.157	Highly Destabilizing	1.0	D	0.863	deleterious	D	0.529483207	None	None	N
V/E	0.9882	likely_pathogenic	0.9904	pathogenic	-2.888	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
V/F	0.8711	likely_pathogenic	0.8501	pathogenic	-1.278	Destabilizing	1.0	D	0.851	deleterious	D	0.529229717	None	None	N
V/G	0.8202	likely_pathogenic	0.8172	pathogenic	-2.943	Highly Destabilizing	1.0	D	0.845	deleterious	N	0.494996217	None	None	N
V/H	0.9978	likely_pathogenic	0.9981	pathogenic	-2.586	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/I	0.1411	likely_benign	0.1384	benign	-0.864	Destabilizing	0.997	D	0.55	neutral	D	0.527733869	None	None	N
V/K	0.993	likely_pathogenic	0.9945	pathogenic	-1.731	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
V/L	0.7054	likely_pathogenic	0.7129	pathogenic	-0.864	Destabilizing	0.997	D	0.626	neutral	N	0.501464224	None	None	N
V/M	0.7282	likely_pathogenic	0.7298	pathogenic	-1.365	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
V/N	0.9889	likely_pathogenic	0.9903	pathogenic	-2.259	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/P	0.9976	likely_pathogenic	0.9976	pathogenic	-1.359	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
V/Q	0.9898	likely_pathogenic	0.9911	pathogenic	-2.007	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/R	0.9866	likely_pathogenic	0.9881	pathogenic	-1.724	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/S	0.9438	likely_pathogenic	0.9447	pathogenic	-2.804	Highly Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
V/T	0.8602	likely_pathogenic	0.8706	pathogenic	-2.39	Highly Destabilizing	0.999	D	0.613	neutral	None	None	None	None	N
V/W	0.9983	likely_pathogenic	0.9983	pathogenic	-1.715	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
V/Y	0.987	likely_pathogenic	0.986	pathogenic	-1.455	Destabilizing	1.0	D	0.852	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.