TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17982	54169;54170;54171	chr2:178605233;178605232;178605231	chr2:179469960;179469959;179469958
N2AB	16341	49246;49247;49248	chr2:178605233;178605232;178605231	chr2:179469960;179469959;179469958
N2A	15414	46465;46466;46467	chr2:178605233;178605232;178605231	chr2:179469960;179469959;179469958
N2B	8917	26974;26975;26976	chr2:178605233;178605232;178605231	chr2:179469960;179469959;179469958
Novex-1	9042	27349;27350;27351	chr2:178605233;178605232;178605231	chr2:179469960;179469959;179469958
Novex-2	9109	27550;27551;27552	chr2:178605233;178605232;178605231	chr2:179469960;179469959;179469958
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-114
• Domain position: 15
• Structural Position: 25
• Q(SASA): 0.3922
• 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
E/K	rs1270287250	0.114	0.885	N	0.381	0.198	0.260735089382	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.1489E-04	0	None	0	0	None	0	None	0	0	0
E/K	rs1270287250	0.114	0.885	N	0.381	0.198	0.260735089382	gnomAD-3.1.2	6.59E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs1270287250	0.114	0.885	N	0.381	0.198	0.260735089382	gnomAD-4.0.0	3.04585E-06	None	None	None	None	N	None	3.49846E-05	0	None	0	0	None	0	0	1.2051E-06	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	0.2809	likely_benign	0.2944	benign	-0.646	Destabilizing	0.939	D	0.379	neutral	N	0.472431507	None	None	N
E/C	0.9009	likely_pathogenic	0.8997	pathogenic	-0.245	Destabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	N
E/D	0.1402	likely_benign	0.1344	benign	-0.654	Destabilizing	0.02	N	0.181	neutral	N	0.450341294	None	None	N
E/F	0.8437	likely_pathogenic	0.8307	pathogenic	-0.369	Destabilizing	0.999	D	0.617	neutral	None	None	None	None	N
E/G	0.3877	ambiguous	0.3871	ambiguous	-0.908	Destabilizing	0.939	D	0.435	neutral	N	0.477855969	None	None	N
E/H	0.6808	likely_pathogenic	0.6561	pathogenic	-0.359	Destabilizing	0.998	D	0.361	neutral	None	None	None	None	N
E/I	0.5398	ambiguous	0.5626	ambiguous	0.036	Stabilizing	0.993	D	0.625	neutral	None	None	None	None	N
E/K	0.3632	ambiguous	0.3578	ambiguous	-0.11	Destabilizing	0.885	D	0.381	neutral	N	0.487187529	None	None	N
E/L	0.5788	likely_pathogenic	0.5987	pathogenic	0.036	Stabilizing	0.986	D	0.588	neutral	None	None	None	None	N
E/M	0.5291	ambiguous	0.5393	ambiguous	0.258	Stabilizing	0.998	D	0.563	neutral	None	None	None	None	N
E/N	0.3173	likely_benign	0.3259	benign	-0.487	Destabilizing	0.986	D	0.349	neutral	None	None	None	None	N
E/P	0.9895	likely_pathogenic	0.9892	pathogenic	-0.17	Destabilizing	0.993	D	0.435	neutral	None	None	None	None	N
E/Q	0.2083	likely_benign	0.2106	benign	-0.423	Destabilizing	0.322	N	0.257	neutral	N	0.461078363	None	None	N
E/R	0.6099	likely_pathogenic	0.5861	pathogenic	0.145	Stabilizing	0.973	D	0.374	neutral	None	None	None	None	N
E/S	0.2775	likely_benign	0.2842	benign	-0.683	Destabilizing	0.953	D	0.343	neutral	None	None	None	None	N
E/T	0.3166	likely_benign	0.3357	benign	-0.473	Destabilizing	0.986	D	0.371	neutral	None	None	None	None	N
E/V	0.3625	ambiguous	0.3832	ambiguous	-0.17	Destabilizing	0.991	D	0.519	neutral	N	0.461344562	None	None	N
E/W	0.9703	likely_pathogenic	0.9632	pathogenic	-0.164	Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	N
E/Y	0.7694	likely_pathogenic	0.755	pathogenic	-0.129	Destabilizing	0.998	D	0.565	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.