TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15769	47530;47531;47532	chr2:178618046;178618045;178618044	chr2:179482773;179482772;179482771
N2AB	14128	42607;42608;42609	chr2:178618046;178618045;178618044	chr2:179482773;179482772;179482771
N2A	13201	39826;39827;39828	chr2:178618046;178618045;178618044	chr2:179482773;179482772;179482771
N2B	6704	20335;20336;20337	chr2:178618046;178618045;178618044	chr2:179482773;179482772;179482771
Novex-1	6829	20710;20711;20712	chr2:178618046;178618045;178618044	chr2:179482773;179482772;179482771
Novex-2	6896	20911;20912;20913	chr2:178618046;178618045;178618044	chr2:179482773;179482772;179482771
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: Fn3-2
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.5387
• 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/H	None	None	1.0	D	0.671	0.387	0.348983352498	gnomAD-4.0.0	1.59432E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43365E-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
D/A	0.1533	likely_benign	0.1757	benign	-0.239	Destabilizing	0.999	D	0.589	neutral	N	0.495944986	None	None	N
D/C	0.6644	likely_pathogenic	0.6903	pathogenic	0.184	Stabilizing	1.0	D	0.657	neutral	None	None	None	None	N
D/E	0.153	likely_benign	0.1649	benign	-0.265	Destabilizing	0.992	D	0.399	neutral	N	0.465999278	None	None	N
D/F	0.6792	likely_pathogenic	0.7018	pathogenic	-0.292	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
D/G	0.1452	likely_benign	0.1863	benign	-0.425	Destabilizing	0.992	D	0.541	neutral	D	0.547683761	None	None	N
D/H	0.2909	likely_benign	0.286	benign	-0.219	Destabilizing	1.0	D	0.671	neutral	D	0.57820511	None	None	N
D/I	0.5296	ambiguous	0.5579	ambiguous	0.195	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
D/K	0.3814	ambiguous	0.3871	ambiguous	0.432	Stabilizing	0.998	D	0.651	neutral	None	None	None	None	N
D/L	0.4945	ambiguous	0.5248	ambiguous	0.195	Stabilizing	0.999	D	0.692	prob.neutral	None	None	None	None	N
D/M	0.6455	likely_pathogenic	0.6784	pathogenic	0.394	Stabilizing	1.0	D	0.641	neutral	None	None	None	None	N
D/N	0.0925	likely_benign	0.0941	benign	0.169	Stabilizing	0.619	D	0.196	neutral	N	0.479442455	None	None	N
D/P	0.9214	likely_pathogenic	0.9298	pathogenic	0.073	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
D/Q	0.3164	likely_benign	0.3421	ambiguous	0.194	Stabilizing	0.999	D	0.653	neutral	None	None	None	None	N
D/R	0.3905	ambiguous	0.3975	ambiguous	0.492	Stabilizing	0.999	D	0.659	neutral	None	None	None	None	N
D/S	0.1085	likely_benign	0.1178	benign	0.073	Stabilizing	0.994	D	0.514	neutral	None	None	None	None	N
D/T	0.2385	likely_benign	0.2551	benign	0.218	Stabilizing	0.998	D	0.637	neutral	None	None	None	None	N
D/V	0.32	likely_benign	0.3359	benign	0.073	Stabilizing	1.0	D	0.695	prob.neutral	D	0.534297927	None	None	N
D/W	0.8978	likely_pathogenic	0.8927	pathogenic	-0.196	Destabilizing	1.0	D	0.658	neutral	None	None	None	None	N
D/Y	0.3345	likely_benign	0.3193	benign	-0.06	Destabilizing	1.0	D	0.649	neutral	D	0.625030617	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.