TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31279	94060;94061;94062	chr2:178547791;178547790;178547789	chr2:179412518;179412517;179412516
N2AB	29638	89137;89138;89139	chr2:178547791;178547790;178547789	chr2:179412518;179412517;179412516
N2A	28711	86356;86357;86358	chr2:178547791;178547790;178547789	chr2:179412518;179412517;179412516
N2B	22214	66865;66866;66867	chr2:178547791;178547790;178547789	chr2:179412518;179412517;179412516
Novex-1	22339	67240;67241;67242	chr2:178547791;178547790;178547789	chr2:179412518;179412517;179412516
Novex-2	22406	67441;67442;67443	chr2:178547791;178547790;178547789	chr2:179412518;179412517;179412516
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-151
• Domain position: 62
• Structural Position: 145
• Q(SASA): 0.5649
• 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
M/I	rs577904312	0.417	0.969	N	0.235	0.242	0.387850303812	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
M/I	rs577904312	0.417	0.969	N	0.235	0.242	0.387850303812	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
M/I	rs577904312	0.417	0.969	N	0.235	0.242	0.387850303812	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
M/I	rs577904312	0.417	0.969	N	0.235	0.242	0.387850303812	gnomAD-4.0.0	6.56625E-06	None	None	None	None	N	None	2.40523E-05	0	None	0	0	None	0	0	0	0	0
M/L	None	None	0.652	N	0.231	0.295	0.395143324098	gnomAD-4.0.0	6.84173E-07	None	None	None	None	N	None	0	0	None	0	2.51991E-05	None	0	0	0	0	0
M/T	None	None	0.912	N	0.327	0.318	0.691401027782	gnomAD-4.0.0	1.59105E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85776E-06	0	0
M/V	rs765117891	0.327	0.811	N	0.305	0.272	0.369867359543	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	1.14811E-04	0	None	0	0	None	0	None	0	0	0
M/V	rs765117891	0.327	0.811	N	0.305	0.272	0.369867359543	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	1.47E-05	0	0
M/V	rs765117891	0.327	0.811	N	0.305	0.272	0.369867359543	gnomAD-4.0.0	7.43576E-06	None	None	None	None	N	None	1.33444E-05	0	None	0	0	None	0	0	8.47565E-06	0	1.60097E-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
M/A	0.2984	likely_benign	0.3508	ambiguous	-0.736	Destabilizing	0.737	D	0.369	neutral	None	None	None	None	N
M/C	0.5919	likely_pathogenic	0.5889	pathogenic	-0.609	Destabilizing	0.998	D	0.379	neutral	None	None	None	None	N
M/D	0.7536	likely_pathogenic	0.7982	pathogenic	0.144	Stabilizing	0.932	D	0.421	neutral	None	None	None	None	N
M/E	0.3682	ambiguous	0.4004	ambiguous	0.097	Stabilizing	0.737	D	0.349	neutral	None	None	None	None	N
M/F	0.3487	ambiguous	0.362	ambiguous	-0.351	Destabilizing	0.993	D	0.333	neutral	None	None	None	None	N
M/G	0.4569	ambiguous	0.5125	ambiguous	-0.938	Destabilizing	0.932	D	0.387	neutral	None	None	None	None	N
M/H	0.3689	ambiguous	0.3904	ambiguous	-0.096	Destabilizing	0.993	D	0.362	neutral	None	None	None	None	N
M/I	0.3413	ambiguous	0.3692	ambiguous	-0.29	Destabilizing	0.969	D	0.235	neutral	N	0.456713559	None	None	N
M/K	0.1152	likely_benign	0.1234	benign	0.334	Stabilizing	0.01	N	0.131	neutral	N	0.378692706	None	None	N
M/L	0.0951	likely_benign	0.1087	benign	-0.29	Destabilizing	0.652	D	0.231	neutral	N	0.432567263	None	None	N
M/N	0.4025	ambiguous	0.4474	ambiguous	0.49	Stabilizing	0.932	D	0.398	neutral	None	None	None	None	N
M/P	0.8882	likely_pathogenic	0.9204	pathogenic	-0.409	Destabilizing	0.977	D	0.379	neutral	None	None	None	None	N
M/Q	0.1341	likely_benign	0.1419	benign	0.296	Stabilizing	0.872	D	0.223	neutral	None	None	None	None	N
M/R	0.1426	likely_benign	0.154	benign	0.827	Stabilizing	0.514	D	0.333	neutral	N	0.441936108	None	None	N
M/S	0.2669	likely_benign	0.2895	benign	-0.02	Destabilizing	0.737	D	0.335	neutral	None	None	None	None	N
M/T	0.1707	likely_benign	0.1922	benign	0.038	Stabilizing	0.912	D	0.327	neutral	N	0.415018865	None	None	N
M/V	0.079	likely_benign	0.0866	benign	-0.409	Destabilizing	0.811	D	0.305	neutral	N	0.415058937	None	None	N
M/W	0.6728	likely_pathogenic	0.698	pathogenic	-0.288	Destabilizing	0.998	D	0.394	neutral	None	None	None	None	N
M/Y	0.561	ambiguous	0.5734	pathogenic	-0.15	Destabilizing	0.993	D	0.403	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.