TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24869	74830;74831;74832	chr2:178571527;178571526;178571525	chr2:179436254;179436253;179436252
N2AB	23228	69907;69908;69909	chr2:178571527;178571526;178571525	chr2:179436254;179436253;179436252
N2A	22301	67126;67127;67128	chr2:178571527;178571526;178571525	chr2:179436254;179436253;179436252
N2B	15804	47635;47636;47637	chr2:178571527;178571526;178571525	chr2:179436254;179436253;179436252
Novex-1	15929	48010;48011;48012	chr2:178571527;178571526;178571525	chr2:179436254;179436253;179436252
Novex-2	15996	48211;48212;48213	chr2:178571527;178571526;178571525	chr2:179436254;179436253;179436252
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-68
• Domain position: 62
• Structural Position: 92
• Q(SASA): 0.5773
• 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
K/N	rs1708181075	None	0.988	N	0.698	0.272	0.203808441222	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	0	4.78011E-04
K/N	rs1708181075	None	0.988	N	0.698	0.272	0.203808441222	gnomAD-4.0.0	6.5767E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	4.78011E-04

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
K/A	0.9768	likely_pathogenic	0.9739	pathogenic	-0.321	Destabilizing	0.968	D	0.629	neutral	None	None	None	None	N
K/C	0.9795	likely_pathogenic	0.9776	pathogenic	-0.415	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
K/D	0.9947	likely_pathogenic	0.9943	pathogenic	0.011	Stabilizing	0.995	D	0.766	deleterious	None	None	None	None	N
K/E	0.9587	likely_pathogenic	0.9543	pathogenic	0.055	Stabilizing	0.958	D	0.549	neutral	N	0.464999229	None	None	N
K/F	0.995	likely_pathogenic	0.994	pathogenic	-0.354	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
K/G	0.9883	likely_pathogenic	0.9873	pathogenic	-0.603	Destabilizing	0.991	D	0.686	prob.neutral	None	None	None	None	N
K/H	0.8121	likely_pathogenic	0.8067	pathogenic	-0.986	Destabilizing	0.999	D	0.734	prob.delet.	None	None	None	None	N
K/I	0.9475	likely_pathogenic	0.939	pathogenic	0.364	Stabilizing	0.995	D	0.742	deleterious	None	None	None	None	N
K/L	0.9417	likely_pathogenic	0.937	pathogenic	0.364	Stabilizing	0.991	D	0.686	prob.neutral	None	None	None	None	N
K/M	0.9067	likely_pathogenic	0.8967	pathogenic	0.344	Stabilizing	0.999	D	0.736	prob.delet.	N	0.480838986	None	None	N
K/N	0.9853	likely_pathogenic	0.9844	pathogenic	-0.1	Destabilizing	0.988	D	0.698	prob.neutral	N	0.467899291	None	None	N
K/P	0.9923	likely_pathogenic	0.9911	pathogenic	0.166	Stabilizing	0.998	D	0.766	deleterious	None	None	None	None	N
K/Q	0.739	likely_pathogenic	0.7175	pathogenic	-0.31	Destabilizing	0.988	D	0.683	prob.neutral	N	0.471355558	None	None	N
K/R	0.1414	likely_benign	0.1312	benign	-0.301	Destabilizing	0.142	N	0.324	neutral	N	0.485022376	None	None	N
K/S	0.9806	likely_pathogenic	0.9794	pathogenic	-0.732	Destabilizing	0.968	D	0.623	neutral	None	None	None	None	N
K/T	0.8811	likely_pathogenic	0.8702	pathogenic	-0.51	Destabilizing	0.988	D	0.758	deleterious	N	0.442476746	None	None	N
K/V	0.9308	likely_pathogenic	0.9221	pathogenic	0.166	Stabilizing	0.995	D	0.74	deleterious	None	None	None	None	N
K/W	0.989	likely_pathogenic	0.9861	pathogenic	-0.239	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
K/Y	0.981	likely_pathogenic	0.9784	pathogenic	0.091	Stabilizing	0.998	D	0.746	deleterious	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.