TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35209	105850;105851;105852	chr2:178530990;178530989;178530988	chr2:179395717;179395716;179395715
N2AB	33568	100927;100928;100929	chr2:178530990;178530989;178530988	chr2:179395717;179395716;179395715
N2A	32641	98146;98147;98148	chr2:178530990;178530989;178530988	chr2:179395717;179395716;179395715
N2B	26144	78655;78656;78657	chr2:178530990;178530989;178530988	chr2:179395717;179395716;179395715
Novex-1	26269	79030;79031;79032	chr2:178530990;178530989;178530988	chr2:179395717;179395716;179395715
Novex-2	26336	79231;79232;79233	chr2:178530990;178530989;178530988	chr2:179395717;179395716;179395715
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-164
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.6158
• 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/Q	rs56365812	0.167	0.025	N	0.489	0.133	0.207176502487	gnomAD-2.1.1	1.2E-05	None	None	None	None	N	None	0	0	None	0	1.66889E-04	None	0	None	0	0	0
K/Q	rs56365812	0.167	0.025	N	0.489	0.133	0.207176502487	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	5.76923E-04	None	0	0	0	0	0
K/Q	rs56365812	0.167	0.025	N	0.489	0.133	0.207176502487	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	1E-03	0	None	None	None	0	None
K/Q	rs56365812	0.167	0.025	N	0.489	0.133	0.207176502487	gnomAD-4.0.0	4.95663E-06	None	None	None	None	N	None	0	0	None	0	1.33666E-04	None	0	0	0	0	3.20061E-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
K/A	0.3049	likely_benign	0.3845	ambiguous	-0.141	Destabilizing	0.014	N	0.494	neutral	None	None	None	None	N
K/C	0.5549	ambiguous	0.6295	pathogenic	-0.34	Destabilizing	0.646	D	0.577	neutral	None	None	None	None	N
K/D	0.6711	likely_pathogenic	0.7447	pathogenic	-0.011	Destabilizing	0.064	N	0.503	neutral	None	None	None	None	N
K/E	0.1832	likely_benign	0.2169	benign	0.04	Stabilizing	0.025	N	0.446	neutral	N	0.381370438	None	None	N
K/F	0.6473	likely_pathogenic	0.7067	pathogenic	-0.052	Destabilizing	0.326	N	0.573	neutral	None	None	None	None	N
K/G	0.4402	ambiguous	0.5305	ambiguous	-0.427	Destabilizing	0.064	N	0.545	neutral	None	None	None	None	N
K/H	0.2933	likely_benign	0.3231	benign	-0.712	Destabilizing	0.326	N	0.519	neutral	None	None	None	None	N
K/I	0.25	likely_benign	0.3113	benign	0.558	Stabilizing	0.083	N	0.575	neutral	N	0.507107881	None	None	N
K/L	0.2631	likely_benign	0.3441	ambiguous	0.558	Stabilizing	0.033	N	0.551	neutral	None	None	None	None	N
K/M	0.1735	likely_benign	0.2258	benign	0.291	Stabilizing	0.326	N	0.518	neutral	None	None	None	None	N
K/N	0.3876	ambiguous	0.4639	ambiguous	-0.057	Destabilizing	0.049	N	0.453	neutral	N	0.478401127	None	None	N
K/P	0.7944	likely_pathogenic	0.9049	pathogenic	0.356	Stabilizing	0.326	N	0.513	neutral	None	None	None	None	N
K/Q	0.1192	likely_benign	0.1312	benign	-0.191	Destabilizing	0.025	N	0.489	neutral	N	0.474686031	None	None	N
K/R	0.0677	likely_benign	0.0728	benign	-0.291	Destabilizing	None	N	0.146	neutral	N	0.429031099	None	None	N
K/S	0.3205	likely_benign	0.3935	ambiguous	-0.593	Destabilizing	0.033	N	0.411	neutral	None	None	None	None	N
K/T	0.1053	likely_benign	0.143	benign	-0.368	Destabilizing	None	N	0.295	neutral	N	0.45956465	None	None	N
K/V	0.2497	likely_benign	0.3061	benign	0.356	Stabilizing	0.033	N	0.538	neutral	None	None	None	None	N
K/W	0.6281	likely_pathogenic	0.6872	pathogenic	0.004	Stabilizing	0.848	D	0.635	neutral	None	None	None	None	N
K/Y	0.5412	ambiguous	0.6089	pathogenic	0.31	Stabilizing	0.326	N	0.572	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.