TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23509	70750;70751;70752	chr2:178575607;178575606;178575605	chr2:179440334;179440333;179440332
N2AB	21868	65827;65828;65829	chr2:178575607;178575606;178575605	chr2:179440334;179440333;179440332
N2A	20941	63046;63047;63048	chr2:178575607;178575606;178575605	chr2:179440334;179440333;179440332
N2B	14444	43555;43556;43557	chr2:178575607;178575606;178575605	chr2:179440334;179440333;179440332
Novex-1	14569	43930;43931;43932	chr2:178575607;178575606;178575605	chr2:179440334;179440333;179440332
Novex-2	14636	44131;44132;44133	chr2:178575607;178575606;178575605	chr2:179440334;179440333;179440332
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-58
• Domain position: 75
• Structural Position: 108
• Q(SASA): 0.0806
• 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/E	rs926271333	None	1.0	D	0.875	0.873	0.905623151949	gnomAD-4.0.0	6.8427E-07	None	None	None	None	N	None	2.98846E-05	0	None	0	0	None	0	0	0	0	0
V/G	rs926271333	None	1.0	D	0.891	0.864	0.921624639312	gnomAD-4.0.0	6.8427E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99548E-07	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
V/A	0.9243	likely_pathogenic	0.9385	pathogenic	-2.496	Highly Destabilizing	0.999	D	0.595	neutral	D	0.574369131	None	None	N
V/C	0.9771	likely_pathogenic	0.9806	pathogenic	-2.064	Highly Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
V/D	0.9993	likely_pathogenic	0.9995	pathogenic	-3.624	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
V/E	0.9973	likely_pathogenic	0.9978	pathogenic	-3.327	Highly Destabilizing	1.0	D	0.875	deleterious	D	0.655021777	None	None	N
V/F	0.9705	likely_pathogenic	0.9759	pathogenic	-1.422	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
V/G	0.9657	likely_pathogenic	0.9722	pathogenic	-3.08	Highly Destabilizing	1.0	D	0.891	deleterious	D	0.655021777	None	None	N
V/H	0.9995	likely_pathogenic	0.9995	pathogenic	-2.917	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
V/I	0.1188	likely_benign	0.1333	benign	-0.797	Destabilizing	0.722	D	0.265	neutral	None	None	None	None	N
V/K	0.9981	likely_pathogenic	0.9982	pathogenic	-2.214	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/L	0.8091	likely_pathogenic	0.8442	pathogenic	-0.797	Destabilizing	0.922	D	0.494	neutral	D	0.530813106	None	None	N
V/M	0.9054	likely_pathogenic	0.9241	pathogenic	-0.996	Destabilizing	1.0	D	0.701	prob.neutral	D	0.567874671	None	None	N
V/N	0.9967	likely_pathogenic	0.9974	pathogenic	-2.824	Highly Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
V/P	0.9979	likely_pathogenic	0.9983	pathogenic	-1.346	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
V/Q	0.9974	likely_pathogenic	0.9977	pathogenic	-2.533	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
V/R	0.9962	likely_pathogenic	0.9964	pathogenic	-2.157	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
V/S	0.986	likely_pathogenic	0.9899	pathogenic	-3.341	Highly Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
V/T	0.9571	likely_pathogenic	0.9665	pathogenic	-2.897	Highly Destabilizing	1.0	D	0.666	neutral	None	None	None	None	N
V/W	0.9997	likely_pathogenic	0.9998	pathogenic	-2.049	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
V/Y	0.9979	likely_pathogenic	0.9981	pathogenic	-1.725	Destabilizing	1.0	D	0.799	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.