TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22768	68527;68528;68529	chr2:178578638;178578637;178578636	chr2:179443365;179443364;179443363
N2AB	21127	63604;63605;63606	chr2:178578638;178578637;178578636	chr2:179443365;179443364;179443363
N2A	20200	60823;60824;60825	chr2:178578638;178578637;178578636	chr2:179443365;179443364;179443363
N2B	13703	41332;41333;41334	chr2:178578638;178578637;178578636	chr2:179443365;179443364;179443363
Novex-1	13828	41707;41708;41709	chr2:178578638;178578637;178578636	chr2:179443365;179443364;179443363
Novex-2	13895	41908;41909;41910	chr2:178578638;178578637;178578636	chr2:179443365;179443364;179443363
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: Fn3-53
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.8693
• Predicted PPI site: I

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	None	None	0.002	N	0.303	0.076	0.107399877778	gnomAD-4.0.0	6.85087E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.16371E-05	0
K/R	rs761210578	0.203	None	N	0.161	0.112	0.0551355673512	gnomAD-2.1.1	7.19E-06	None	None	None	None	I	None	8.3E-05	0	None	0	0	None	0	None	0	0	0
K/R	rs761210578	0.203	None	N	0.161	0.112	0.0551355673512	gnomAD-3.1.2	3.29E-05	None	None	None	None	I	None	1.20645E-04	0	0	0	0	None	0	0	0	0	0
K/R	rs761210578	0.203	None	N	0.161	0.112	0.0551355673512	gnomAD-4.0.0	5.58341E-06	None	None	None	None	I	None	1.06886E-04	0	None	0	0	None	0	0	8.48194E-07	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
K/A	0.2777	likely_benign	0.2476	benign	0.077	Stabilizing	0.002	N	0.231	neutral	None	None	None	None	I
K/C	0.5567	ambiguous	0.473	ambiguous	-0.254	Destabilizing	0.935	D	0.289	neutral	None	None	None	None	I
K/D	0.5485	ambiguous	0.5128	ambiguous	-0.075	Destabilizing	0.001	N	0.238	neutral	None	None	None	None	I
K/E	0.1873	likely_benign	0.1721	benign	-0.07	Destabilizing	0.027	N	0.369	neutral	N	0.433324119	None	None	I
K/F	0.6887	likely_pathogenic	0.6283	pathogenic	-0.124	Destabilizing	0.555	D	0.329	neutral	None	None	None	None	I
K/G	0.3125	likely_benign	0.2544	benign	-0.107	Destabilizing	0.067	N	0.364	neutral	None	None	None	None	I
K/H	0.2758	likely_benign	0.2372	benign	-0.273	Destabilizing	0.555	D	0.349	neutral	None	None	None	None	I
K/I	0.309	likely_benign	0.2886	benign	0.483	Stabilizing	0.555	D	0.371	neutral	None	None	None	None	I
K/L	0.2824	likely_benign	0.2493	benign	0.483	Stabilizing	0.149	N	0.463	neutral	None	None	None	None	I
K/M	0.2495	likely_benign	0.2331	benign	0.12	Stabilizing	0.741	D	0.341	neutral	N	0.487006675	None	None	I
K/N	0.4287	ambiguous	0.4021	ambiguous	0.194	Stabilizing	0.002	N	0.303	neutral	N	0.462975023	None	None	I
K/P	0.4493	ambiguous	0.4163	ambiguous	0.374	Stabilizing	0.555	D	0.385	neutral	None	None	None	None	I
K/Q	0.1187	likely_benign	0.1068	benign	0.041	Stabilizing	0.062	N	0.371	neutral	N	0.455528975	None	None	I
K/R	0.063	likely_benign	0.0567	benign	-0.025	Destabilizing	None	N	0.161	neutral	N	0.459145284	None	None	I
K/S	0.3704	ambiguous	0.333	benign	-0.227	Destabilizing	0.035	N	0.339	neutral	None	None	None	None	I
K/T	0.2043	likely_benign	0.197	benign	-0.085	Destabilizing	0.117	N	0.436	neutral	N	0.426918222	None	None	I
K/V	0.2656	likely_benign	0.2396	benign	0.374	Stabilizing	0.149	N	0.441	neutral	None	None	None	None	I
K/W	0.5866	likely_pathogenic	0.4637	ambiguous	-0.18	Destabilizing	0.935	D	0.37	neutral	None	None	None	None	I
K/Y	0.5412	ambiguous	0.478	ambiguous	0.168	Stabilizing	0.555	D	0.361	neutral	None	None	None	None	I

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.