TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32574	97945;97946;97947	chr2:178541357;178541356;178541355	chr2:179406084;179406083;179406082
N2AB	30933	93022;93023;93024	chr2:178541357;178541356;178541355	chr2:179406084;179406083;179406082
N2A	30006	90241;90242;90243	chr2:178541357;178541356;178541355	chr2:179406084;179406083;179406082
N2B	23509	70750;70751;70752	chr2:178541357;178541356;178541355	chr2:179406084;179406083;179406082
Novex-1	23634	71125;71126;71127	chr2:178541357;178541356;178541355	chr2:179406084;179406083;179406082
Novex-2	23701	71326;71327;71328	chr2:178541357;178541356;178541355	chr2:179406084;179406083;179406082
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: Fn3-125
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.094
• 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/F	None	None	0.782	D	0.721	0.667	0.72613263291	gnomAD-4.0.0	6.92741E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.67543E-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	0.6641	likely_pathogenic	0.7128	pathogenic	-2.431	Highly Destabilizing	0.296	N	0.577	neutral	D	0.555935708	None	None	N
V/C	0.9465	likely_pathogenic	0.9461	pathogenic	-2.018	Highly Destabilizing	0.991	D	0.743	deleterious	None	None	None	None	N
V/D	0.9966	likely_pathogenic	0.9971	pathogenic	-3.402	Highly Destabilizing	0.879	D	0.865	deleterious	D	0.638538087	None	None	N
V/E	0.9901	likely_pathogenic	0.9918	pathogenic	-3.113	Highly Destabilizing	0.906	D	0.832	deleterious	None	None	None	None	N
V/F	0.8639	likely_pathogenic	0.8988	pathogenic	-1.329	Destabilizing	0.782	D	0.721	prob.delet.	D	0.562683658	None	None	N
V/G	0.8791	likely_pathogenic	0.8965	pathogenic	-3.009	Highly Destabilizing	0.879	D	0.851	deleterious	D	0.638538087	None	None	N
V/H	0.9979	likely_pathogenic	0.9983	pathogenic	-2.839	Highly Destabilizing	0.991	D	0.871	deleterious	None	None	None	None	N
V/I	0.1181	likely_benign	0.1255	benign	-0.761	Destabilizing	0.001	N	0.189	neutral	D	0.53231297	None	None	N
V/K	0.9945	likely_pathogenic	0.9952	pathogenic	-1.998	Destabilizing	0.906	D	0.833	deleterious	None	None	None	None	N
V/L	0.6633	likely_pathogenic	0.7101	pathogenic	-0.761	Destabilizing	0.031	N	0.318	neutral	N	0.519950553	None	None	N
V/M	0.7069	likely_pathogenic	0.75	pathogenic	-1.061	Destabilizing	0.826	D	0.615	neutral	None	None	None	None	N
V/N	0.9866	likely_pathogenic	0.989	pathogenic	-2.569	Highly Destabilizing	0.967	D	0.883	deleterious	None	None	None	None	N
V/P	0.9931	likely_pathogenic	0.994	pathogenic	-1.298	Destabilizing	0.967	D	0.844	deleterious	None	None	None	None	N
V/Q	0.9901	likely_pathogenic	0.9918	pathogenic	-2.276	Highly Destabilizing	0.967	D	0.869	deleterious	None	None	None	None	N
V/R	0.9877	likely_pathogenic	0.9895	pathogenic	-1.963	Destabilizing	0.906	D	0.881	deleterious	None	None	None	None	N
V/S	0.9315	likely_pathogenic	0.944	pathogenic	-3.102	Highly Destabilizing	0.906	D	0.793	deleterious	None	None	None	None	N
V/T	0.8399	likely_pathogenic	0.8587	pathogenic	-2.668	Highly Destabilizing	0.575	D	0.595	neutral	None	None	None	None	N
V/W	0.9984	likely_pathogenic	0.9987	pathogenic	-1.931	Destabilizing	0.991	D	0.849	deleterious	None	None	None	None	N
V/Y	0.99	likely_pathogenic	0.9921	pathogenic	-1.616	Destabilizing	0.906	D	0.72	prob.delet.	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.