TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25548	76867;76868;76869	chr2:178569490;178569489;178569488	chr2:179434217;179434216;179434215
N2AB	23907	71944;71945;71946	chr2:178569490;178569489;178569488	chr2:179434217;179434216;179434215
N2A	22980	69163;69164;69165	chr2:178569490;178569489;178569488	chr2:179434217;179434216;179434215
N2B	16483	49672;49673;49674	chr2:178569490;178569489;178569488	chr2:179434217;179434216;179434215
Novex-1	16608	50047;50048;50049	chr2:178569490;178569489;178569488	chr2:179434217;179434216;179434215
Novex-2	16675	50248;50249;50250	chr2:178569490;178569489;178569488	chr2:179434217;179434216;179434215
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-135
• Domain position: 35
• Structural Position: 52
• Q(SASA): 1.0854
• 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
D/V	None	None	0.983	N	0.634	0.459	0.410603549233	gnomAD-4.0.0	1.59375E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86334E-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
D/A	0.1478	likely_benign	0.1508	benign	None	Stabilizing	0.892	D	0.509	neutral	N	0.480165925	None	None	N
D/C	0.5478	ambiguous	0.5617	ambiguous	-0.303	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
D/E	0.1226	likely_benign	0.1107	benign	-0.535	Destabilizing	0.011	N	0.285	neutral	N	0.450551938	None	None	N
D/F	0.5236	ambiguous	0.5472	ambiguous	-0.15	Destabilizing	0.999	D	0.621	neutral	None	None	None	None	N
D/G	0.1165	likely_benign	0.117	benign	-0.077	Destabilizing	0.892	D	0.549	neutral	N	0.425607847	None	None	N
D/H	0.2917	likely_benign	0.3038	benign	0.548	Stabilizing	0.995	D	0.571	neutral	N	0.464708243	None	None	N
D/I	0.3624	ambiguous	0.3589	ambiguous	0.135	Stabilizing	0.987	D	0.632	neutral	None	None	None	None	N
D/K	0.4045	ambiguous	0.3841	ambiguous	0.288	Stabilizing	0.845	D	0.548	neutral	None	None	None	None	N
D/L	0.3597	ambiguous	0.3614	ambiguous	0.135	Stabilizing	0.975	D	0.625	neutral	None	None	None	None	N
D/M	0.5386	ambiguous	0.5377	ambiguous	-0.109	Destabilizing	0.999	D	0.643	neutral	None	None	None	None	N
D/N	0.098	likely_benign	0.0988	benign	0.081	Stabilizing	0.967	D	0.599	neutral	N	0.468790982	None	None	N
D/P	0.6033	likely_pathogenic	0.6099	pathogenic	0.106	Stabilizing	0.987	D	0.592	neutral	None	None	None	None	N
D/Q	0.3271	likely_benign	0.3233	benign	0.057	Stabilizing	0.95	D	0.629	neutral	None	None	None	None	N
D/R	0.448	ambiguous	0.4372	ambiguous	0.532	Stabilizing	0.975	D	0.569	neutral	None	None	None	None	N
D/S	0.117	likely_benign	0.122	benign	-0.007	Destabilizing	0.916	D	0.545	neutral	None	None	None	None	N
D/T	0.2161	likely_benign	0.2202	benign	0.061	Stabilizing	0.975	D	0.579	neutral	None	None	None	None	N
D/V	0.2285	likely_benign	0.2272	benign	0.106	Stabilizing	0.983	D	0.634	neutral	N	0.487927833	None	None	N
D/W	0.8388	likely_pathogenic	0.8486	pathogenic	-0.135	Destabilizing	0.999	D	0.676	prob.neutral	None	None	None	None	N
D/Y	0.233	likely_benign	0.2478	benign	0.063	Stabilizing	0.999	D	0.619	neutral	N	0.499030648	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.