TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19335	58228;58229;58230	chr2:178594491;178594490;178594489	chr2:179459218;179459217;179459216
N2AB	17694	53305;53306;53307	chr2:178594491;178594490;178594489	chr2:179459218;179459217;179459216
N2A	16767	50524;50525;50526	chr2:178594491;178594490;178594489	chr2:179459218;179459217;179459216
N2B	10270	31033;31034;31035	chr2:178594491;178594490;178594489	chr2:179459218;179459217;179459216
Novex-1	10395	31408;31409;31410	chr2:178594491;178594490;178594489	chr2:179459218;179459217;179459216
Novex-2	10462	31609;31610;31611	chr2:178594491;178594490;178594489	chr2:179459218;179459217;179459216
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-28
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.1483
• 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
T/A	rs752763361	None	0.061	N	0.241	0.129	0.141422826196	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
T/I	rs878924097	0.014	0.988	N	0.68	0.357	0.399889258716	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
T/I	rs878924097	0.014	0.988	N	0.68	0.357	0.399889258716	gnomAD-4.0.0	4.77661E-06	None	None	None	None	N	None	0	2.28802E-05	None	0	0	None	0	0	2.86E-06	1.43357E-05	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
T/A	0.1841	likely_benign	0.1158	benign	-1.148	Destabilizing	0.061	N	0.241	neutral	N	0.464111173	None	None	N
T/C	0.4725	ambiguous	0.4128	ambiguous	-0.778	Destabilizing	0.999	D	0.618	neutral	None	None	None	None	N
T/D	0.6503	likely_pathogenic	0.5113	ambiguous	-0.366	Destabilizing	0.969	D	0.627	neutral	None	None	None	None	N
T/E	0.6647	likely_pathogenic	0.4867	ambiguous	-0.271	Destabilizing	0.939	D	0.592	neutral	None	None	None	None	N
T/F	0.7067	likely_pathogenic	0.4835	ambiguous	-1.066	Destabilizing	0.997	D	0.671	neutral	None	None	None	None	N
T/G	0.3253	likely_benign	0.2542	benign	-1.49	Destabilizing	0.02	N	0.453	neutral	None	None	None	None	N
T/H	0.5728	likely_pathogenic	0.4215	ambiguous	-1.66	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	N
T/I	0.5233	ambiguous	0.3223	benign	-0.294	Destabilizing	0.988	D	0.68	prob.neutral	N	0.498877108	None	None	N
T/K	0.633	likely_pathogenic	0.4026	ambiguous	-0.648	Destabilizing	0.134	N	0.449	neutral	N	0.476442965	None	None	N
T/L	0.3596	ambiguous	0.2167	benign	-0.294	Destabilizing	0.939	D	0.587	neutral	None	None	None	None	N
T/M	0.2734	likely_benign	0.16	benign	-0.118	Destabilizing	0.999	D	0.633	neutral	None	None	None	None	N
T/N	0.2376	likely_benign	0.1833	benign	-0.898	Destabilizing	0.969	D	0.63	neutral	None	None	None	None	N
T/P	0.4651	ambiguous	0.3478	ambiguous	-0.546	Destabilizing	0.996	D	0.679	prob.neutral	N	0.518599019	None	None	N
T/Q	0.5409	ambiguous	0.3659	ambiguous	-0.873	Destabilizing	0.982	D	0.674	neutral	None	None	None	None	N
T/R	0.6126	likely_pathogenic	0.3592	ambiguous	-0.628	Destabilizing	0.852	D	0.63	neutral	N	0.46780084	None	None	N
T/S	0.1688	likely_benign	0.1398	benign	-1.265	Destabilizing	0.704	D	0.562	neutral	N	0.449563008	None	None	N
T/V	0.3577	ambiguous	0.2366	benign	-0.546	Destabilizing	0.939	D	0.572	neutral	None	None	None	None	N
T/W	0.8924	likely_pathogenic	0.791	pathogenic	-1.003	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	N
T/Y	0.7149	likely_pathogenic	0.526	ambiguous	-0.735	Destabilizing	0.997	D	0.656	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.