TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22361	67306;67307;67308	chr2:178580206;178580205;178580204	chr2:179444933;179444932;179444931
N2AB	20720	62383;62384;62385	chr2:178580206;178580205;178580204	chr2:179444933;179444932;179444931
N2A	19793	59602;59603;59604	chr2:178580206;178580205;178580204	chr2:179444933;179444932;179444931
N2B	13296	40111;40112;40113	chr2:178580206;178580205;178580204	chr2:179444933;179444932;179444931
Novex-1	13421	40486;40487;40488	chr2:178580206;178580205;178580204	chr2:179444933;179444932;179444931
Novex-2	13488	40687;40688;40689	chr2:178580206;178580205;178580204	chr2:179444933;179444932;179444931
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: Fn3-50
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.307
• Predicted PPI site: I

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/M	None	None	0.884	N	0.651	0.18	0.352048277211	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.8515	likely_pathogenic	0.8245	pathogenic	-1.805	Destabilizing	0.472	N	0.553	neutral	N	0.484529651	None	None	I
V/C	0.9146	likely_pathogenic	0.8988	pathogenic	-1.58	Destabilizing	0.996	D	0.731	prob.delet.	None	None	None	None	I
V/D	0.9895	likely_pathogenic	0.9879	pathogenic	-2.296	Highly Destabilizing	0.984	D	0.809	deleterious	None	None	None	None	I
V/E	0.9784	likely_pathogenic	0.9735	pathogenic	-2.23	Highly Destabilizing	0.939	D	0.771	deleterious	N	0.516205484	None	None	I
V/F	0.5767	likely_pathogenic	0.5409	ambiguous	-1.403	Destabilizing	0.742	D	0.741	deleterious	None	None	None	None	I
V/G	0.8886	likely_pathogenic	0.8822	pathogenic	-2.19	Highly Destabilizing	0.939	D	0.763	deleterious	N	0.517472932	None	None	I
V/H	0.9914	likely_pathogenic	0.9898	pathogenic	-1.852	Destabilizing	0.996	D	0.799	deleterious	None	None	None	None	I
V/I	0.0825	likely_benign	0.077	benign	-0.804	Destabilizing	0.206	N	0.508	neutral	None	None	None	None	I
V/K	0.9813	likely_pathogenic	0.9779	pathogenic	-1.455	Destabilizing	0.854	D	0.767	deleterious	None	None	None	None	I
V/L	0.3198	likely_benign	0.2711	benign	-0.804	Destabilizing	0.001	N	0.217	neutral	N	0.373808882	None	None	I
V/M	0.4477	ambiguous	0.3793	ambiguous	-0.79	Destabilizing	0.884	D	0.651	neutral	N	0.478604622	None	None	I
V/N	0.9628	likely_pathogenic	0.9582	pathogenic	-1.471	Destabilizing	0.984	D	0.811	deleterious	None	None	None	None	I
V/P	0.9281	likely_pathogenic	0.8827	pathogenic	-1.106	Destabilizing	0.984	D	0.789	deleterious	None	None	None	None	I
V/Q	0.9765	likely_pathogenic	0.9729	pathogenic	-1.582	Destabilizing	0.984	D	0.794	deleterious	None	None	None	None	I
V/R	0.9714	likely_pathogenic	0.9698	pathogenic	-1.065	Destabilizing	0.953	D	0.809	deleterious	None	None	None	None	I
V/S	0.942	likely_pathogenic	0.932	pathogenic	-2.005	Highly Destabilizing	0.854	D	0.747	deleterious	None	None	None	None	I
V/T	0.8454	likely_pathogenic	0.8251	pathogenic	-1.822	Destabilizing	0.742	D	0.622	neutral	None	None	None	None	I
V/W	0.9879	likely_pathogenic	0.9841	pathogenic	-1.715	Destabilizing	0.996	D	0.798	deleterious	None	None	None	None	I
V/Y	0.9532	likely_pathogenic	0.9469	pathogenic	-1.374	Destabilizing	0.953	D	0.751	deleterious	None	None	None	None	I

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.