TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25514	76765;76766;76767	chr2:178569592;178569591;178569590	chr2:179434319;179434318;179434317
N2AB	23873	71842;71843;71844	chr2:178569592;178569591;178569590	chr2:179434319;179434318;179434317
N2A	22946	69061;69062;69063	chr2:178569592;178569591;178569590	chr2:179434319;179434318;179434317
N2B	16449	49570;49571;49572	chr2:178569592;178569591;178569590	chr2:179434319;179434318;179434317
Novex-1	16574	49945;49946;49947	chr2:178569592;178569591;178569590	chr2:179434319;179434318;179434317
Novex-2	16641	50146;50147;50148	chr2:178569592;178569591;178569590	chr2:179434319;179434318;179434317
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-135
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.5713
• 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
L/P	rs1553601755	None	0.003	N	0.381	0.212	0.604659335069	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/P	rs1553601755	None	0.003	N	0.381	0.212	0.604659335069	gnomAD-4.0.0	6.57687E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.4708E-05	0	0
L/V	None	None	0.001	N	0.203	0.038	0.141422826196	gnomAD-4.0.0	1.59377E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86134E-06	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
L/A	0.1513	likely_benign	0.1543	benign	-0.392	Destabilizing	0.002	N	0.234	neutral	None	None	None	None	N
L/C	0.5581	ambiguous	0.5798	pathogenic	-0.673	Destabilizing	0.965	D	0.468	neutral	None	None	None	None	N
L/D	0.6641	likely_pathogenic	0.6893	pathogenic	-0.261	Destabilizing	0.561	D	0.537	neutral	None	None	None	None	N
L/E	0.4623	ambiguous	0.469	ambiguous	-0.354	Destabilizing	0.561	D	0.475	neutral	None	None	None	None	N
L/F	0.1629	likely_benign	0.1702	benign	-0.558	Destabilizing	0.818	D	0.379	neutral	None	None	None	None	N
L/G	0.3798	ambiguous	0.3861	ambiguous	-0.501	Destabilizing	0.209	N	0.399	neutral	None	None	None	None	N
L/H	0.2671	likely_benign	0.2926	benign	0.134	Stabilizing	0.965	D	0.495	neutral	None	None	None	None	N
L/I	0.0881	likely_benign	0.0962	benign	-0.227	Destabilizing	0.166	N	0.275	neutral	N	0.444568194	None	None	N
L/K	0.4007	ambiguous	0.3905	ambiguous	-0.293	Destabilizing	0.561	D	0.437	neutral	None	None	None	None	N
L/M	0.0999	likely_benign	0.0856	benign	-0.517	Destabilizing	0.047	N	0.209	neutral	None	None	None	None	N
L/N	0.2967	likely_benign	0.3065	benign	-0.118	Destabilizing	0.561	D	0.567	neutral	None	None	None	None	N
L/P	0.1543	likely_benign	0.2074	benign	-0.254	Destabilizing	0.003	N	0.381	neutral	N	0.444048119	None	None	N
L/Q	0.1822	likely_benign	0.188	benign	-0.311	Destabilizing	0.873	D	0.572	neutral	N	0.443701402	None	None	N
L/R	0.3468	ambiguous	0.3605	ambiguous	0.182	Stabilizing	0.662	D	0.562	neutral	N	0.443701402	None	None	N
L/S	0.1956	likely_benign	0.1988	benign	-0.488	Destabilizing	0.047	N	0.35	neutral	None	None	None	None	N
L/T	0.1669	likely_benign	0.1698	benign	-0.482	Destabilizing	0.345	N	0.366	neutral	None	None	None	None	N
L/V	0.0837	likely_benign	0.0883	benign	-0.254	Destabilizing	0.001	N	0.203	neutral	N	0.444048119	None	None	N
L/W	0.3161	likely_benign	0.3388	benign	-0.591	Destabilizing	0.991	D	0.499	neutral	None	None	None	None	N
L/Y	0.3704	ambiguous	0.384	ambiguous	-0.341	Destabilizing	0.901	D	0.501	neutral	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.