TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22898	68917;68918;68919	chr2:178577734;178577733;178577732	chr2:179442461;179442460;179442459
N2AB	21257	63994;63995;63996	chr2:178577734;178577733;178577732	chr2:179442461;179442460;179442459
N2A	20330	61213;61214;61215	chr2:178577734;178577733;178577732	chr2:179442461;179442460;179442459
N2B	13833	41722;41723;41724	chr2:178577734;178577733;178577732	chr2:179442461;179442460;179442459
Novex-1	13958	42097;42098;42099	chr2:178577734;178577733;178577732	chr2:179442461;179442460;179442459
Novex-2	14025	42298;42299;42300	chr2:178577734;178577733;178577732	chr2:179442461;179442460;179442459
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-54
• Domain position: 58
• Structural Position: 88
• Q(SASA): 0.3733
• 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
E/K	rs1416793414	None	0.024	N	0.315	0.133	0.181679512989	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	0	4.78011E-04
E/K	rs1416793414	None	0.024	N	0.315	0.133	0.181679512989	gnomAD-4.0.0	6.57471E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	4.78011E-04
E/Q	rs1416793414	-0.103	0.055	N	0.327	0.112	0.170165803431	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	1.18203E-03	None	0	0	None	0	None	0	0	0
E/Q	rs1416793414	-0.103	0.055	N	0.327	0.112	0.170165803431	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	6.55E-05	0	0	0	None	0	0	0	0	0
E/Q	rs1416793414	-0.103	0.055	N	0.327	0.112	0.170165803431	gnomAD-4.0.0	6.57471E-06	None	None	None	None	I	None	0	6.54793E-05	None	0	0	None	0	0	0	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
E/A	0.1202	likely_benign	0.1253	benign	-0.249	Destabilizing	0.005	N	0.267	neutral	N	0.477517614	None	None	I
E/C	0.6983	likely_pathogenic	0.7167	pathogenic	-0.376	Destabilizing	0.864	D	0.336	neutral	None	None	None	None	I
E/D	0.0588	likely_benign	0.061	benign	-0.466	Destabilizing	None	N	0.093	neutral	N	0.422339121	None	None	I
E/F	0.5706	likely_pathogenic	0.6294	pathogenic	0.005	Stabilizing	0.628	D	0.36	neutral	None	None	None	None	I
E/G	0.1251	likely_benign	0.1297	benign	-0.453	Destabilizing	None	N	0.22	neutral	N	0.478901693	None	None	I
E/H	0.3347	likely_benign	0.372	ambiguous	0.509	Stabilizing	0.356	N	0.39	neutral	None	None	None	None	I
E/I	0.2826	likely_benign	0.3091	benign	0.257	Stabilizing	0.356	N	0.388	neutral	None	None	None	None	I
E/K	0.1771	likely_benign	0.196	benign	0.164	Stabilizing	0.024	N	0.315	neutral	N	0.48074992	None	None	I
E/L	0.3023	likely_benign	0.3265	benign	0.257	Stabilizing	0.072	N	0.43	neutral	None	None	None	None	I
E/M	0.401	ambiguous	0.4202	ambiguous	0.043	Stabilizing	0.864	D	0.321	neutral	None	None	None	None	I
E/N	0.1156	likely_benign	0.124	benign	-0.26	Destabilizing	0.016	N	0.297	neutral	None	None	None	None	I
E/P	0.6849	likely_pathogenic	0.6775	pathogenic	0.108	Stabilizing	0.136	N	0.42	neutral	None	None	None	None	I
E/Q	0.1482	likely_benign	0.1524	benign	-0.2	Destabilizing	0.055	N	0.327	neutral	N	0.463012308	None	None	I
E/R	0.2727	likely_benign	0.3047	benign	0.566	Stabilizing	0.072	N	0.364	neutral	None	None	None	None	I
E/S	0.1202	likely_benign	0.1247	benign	-0.412	Destabilizing	0.001	N	0.109	neutral	None	None	None	None	I
E/T	0.1587	likely_benign	0.1545	benign	-0.239	Destabilizing	0.016	N	0.352	neutral	None	None	None	None	I
E/V	0.1792	likely_benign	0.1978	benign	0.108	Stabilizing	0.106	N	0.395	neutral	N	0.505821723	None	None	I
E/W	0.8494	likely_pathogenic	0.8724	pathogenic	0.157	Stabilizing	0.864	D	0.356	neutral	None	None	None	None	I
E/Y	0.4087	ambiguous	0.4704	ambiguous	0.248	Stabilizing	0.628	D	0.342	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.