TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25768	77527;77528;77529	chr2:178568830;178568829;178568828	chr2:179433557;179433556;179433555
N2AB	24127	72604;72605;72606	chr2:178568830;178568829;178568828	chr2:179433557;179433556;179433555
N2A	23200	69823;69824;69825	chr2:178568830;178568829;178568828	chr2:179433557;179433556;179433555
N2B	16703	50332;50333;50334	chr2:178568830;178568829;178568828	chr2:179433557;179433556;179433555
Novex-1	16828	50707;50708;50709	chr2:178568830;178568829;178568828	chr2:179433557;179433556;179433555
Novex-2	16895	50908;50909;50910	chr2:178568830;178568829;178568828	chr2:179433557;179433556;179433555
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-75
• Domain position: 71
• Structural Position: 105
• Q(SASA): 0.2414
• 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/I	rs541266544	-0.658	0.134	N	0.505	0.123	0.438170831126	gnomAD-2.1.1	1.10953E-04	None	None	None	None	N	None	0	0	None	0	5.15E-05	None	9.48394E-04	None	0	0	1.40805E-04
L/I	rs541266544	-0.658	0.134	N	0.505	0.123	0.438170831126	gnomAD-3.1.2	5.26E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	1.657E-03	0
L/I	rs541266544	-0.658	0.134	N	0.505	0.123	0.438170831126	1000 genomes	3.99361E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	2E-03	None
L/I	rs541266544	-0.658	0.134	N	0.505	0.123	0.438170831126	gnomAD-4.0.0	6.13697E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.03238E-03	8.00615E-05
L/P	rs572569285	-1.497	0.996	N	0.623	0.338	0.785001498622	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
L/P	rs572569285	-1.497	0.996	N	0.623	0.338	0.785001498622	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07297E-04	0
L/P	rs572569285	-1.497	0.996	N	0.623	0.338	0.785001498622	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
L/P	rs572569285	-1.497	0.996	N	0.623	0.338	0.785001498622	gnomAD-4.0.0	2.56364E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.68147E-05	0
L/V	rs541266544	None	0.704	N	0.612	0.182	0.441844919209	gnomAD-4.0.0	2.73782E-06	None	None	None	None	N	None	0	0	None	0	2.52309E-05	None	0	0	0	0	4.9715E-05

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	0.155	likely_benign	0.1415	benign	-2.268	Highly Destabilizing	0.863	D	0.56	neutral	None	None	None	None	N
L/C	0.3453	ambiguous	0.3367	benign	-1.215	Destabilizing	0.999	D	0.562	neutral	None	None	None	None	N
L/D	0.5127	ambiguous	0.4994	ambiguous	-2.757	Highly Destabilizing	0.982	D	0.61	neutral	None	None	None	None	N
L/E	0.2713	likely_benign	0.2637	benign	-2.488	Highly Destabilizing	0.884	D	0.57	neutral	None	None	None	None	N
L/F	0.1074	likely_benign	0.1031	benign	-1.29	Destabilizing	0.988	D	0.55	neutral	N	0.410063257	None	None	N
L/G	0.408	ambiguous	0.3816	ambiguous	-2.819	Highly Destabilizing	0.969	D	0.604	neutral	None	None	None	None	N
L/H	0.1323	likely_benign	0.1337	benign	-2.477	Highly Destabilizing	0.077	N	0.584	neutral	N	0.453083316	None	None	N
L/I	0.0802	likely_benign	0.0782	benign	-0.648	Destabilizing	0.134	N	0.505	neutral	N	0.414565	None	None	N
L/K	0.2424	likely_benign	0.2381	benign	-1.567	Destabilizing	0.884	D	0.545	neutral	None	None	None	None	N
L/M	0.0866	likely_benign	0.0824	benign	-0.608	Destabilizing	0.991	D	0.575	neutral	None	None	None	None	N
L/N	0.2041	likely_benign	0.1958	benign	-2.042	Highly Destabilizing	0.982	D	0.611	neutral	None	None	None	None	N
L/P	0.9192	likely_pathogenic	0.9067	pathogenic	-1.173	Destabilizing	0.996	D	0.623	neutral	N	0.469634038	None	None	N
L/Q	0.0999	likely_benign	0.102	benign	-1.808	Destabilizing	0.373	N	0.517	neutral	None	None	None	None	N
L/R	0.1736	likely_benign	0.1752	benign	-1.503	Destabilizing	0.976	D	0.589	neutral	N	0.417469232	None	None	N
L/S	0.1284	likely_benign	0.1252	benign	-2.631	Highly Destabilizing	0.939	D	0.545	neutral	None	None	None	None	N
L/T	0.1156	likely_benign	0.1073	benign	-2.223	Highly Destabilizing	0.969	D	0.509	neutral	None	None	None	None	N
L/V	0.0773	likely_benign	0.074	benign	-1.173	Destabilizing	0.704	D	0.612	neutral	N	0.405982802	None	None	N
L/W	0.2158	likely_benign	0.2125	benign	-1.774	Destabilizing	0.999	D	0.651	neutral	None	None	None	None	N
L/Y	0.2271	likely_benign	0.2217	benign	-1.434	Destabilizing	0.982	D	0.548	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.