TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21538	64837;64838;64839	chr2:178585132;178585131;178585130	chr2:179449859;179449858;179449857
N2AB	19897	59914;59915;59916	chr2:178585132;178585131;178585130	chr2:179449859;179449858;179449857
N2A	18970	57133;57134;57135	chr2:178585132;178585131;178585130	chr2:179449859;179449858;179449857
N2B	12473	37642;37643;37644	chr2:178585132;178585131;178585130	chr2:179449859;179449858;179449857
Novex-1	12598	38017;38018;38019	chr2:178585132;178585131;178585130	chr2:179449859;179449858;179449857
Novex-2	12665	38218;38219;38220	chr2:178585132;178585131;178585130	chr2:179449859;179449858;179449857
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-124
• Domain position: 70
• Structural Position: 155
• Q(SASA): 0.1409
• 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
S/G	rs1297730026	None	0.124	N	0.614	0.136	0.239901079897	gnomAD-4.0.0	4.7781E-06	None	None	None	None	N	None	0	0	None	0	8.3227E-05	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
S/A	0.0821	likely_benign	0.0851	benign	-0.814	Destabilizing	0.072	N	0.609	neutral	None	None	None	None	N
S/C	0.0717	likely_benign	0.0734	benign	-0.561	Destabilizing	0.958	D	0.689	prob.neutral	N	0.477279089	None	None	N
S/D	0.5228	ambiguous	0.4767	ambiguous	-1.48	Destabilizing	0.157	N	0.623	neutral	None	None	None	None	N
S/E	0.4614	ambiguous	0.4338	ambiguous	-1.274	Destabilizing	0.157	N	0.627	neutral	None	None	None	None	N
S/F	0.1108	likely_benign	0.1129	benign	-0.629	Destabilizing	0.726	D	0.757	deleterious	None	None	None	None	N
S/G	0.127	likely_benign	0.122	benign	-1.211	Destabilizing	0.124	N	0.614	neutral	N	0.456452583	None	None	N
S/H	0.2519	likely_benign	0.2328	benign	-1.561	Destabilizing	0.832	D	0.704	prob.neutral	None	None	None	None	N
S/I	0.0939	likely_benign	0.0988	benign	0.202	Stabilizing	0.497	N	0.732	prob.delet.	N	0.46438524	None	None	N
S/K	0.6756	likely_pathogenic	0.6422	pathogenic	-0.135	Destabilizing	0.157	N	0.629	neutral	None	None	None	None	N
S/L	0.0691	likely_benign	0.0706	benign	0.202	Stabilizing	0.157	N	0.689	prob.neutral	None	None	None	None	N
S/M	0.1264	likely_benign	0.1358	benign	0.02	Stabilizing	0.968	D	0.697	prob.neutral	None	None	None	None	N
S/N	0.1607	likely_benign	0.1536	benign	-0.846	Destabilizing	0.001	N	0.46	neutral	N	0.470442234	None	None	N
S/P	0.8227	likely_pathogenic	0.8094	pathogenic	-0.102	Destabilizing	0.726	D	0.695	prob.neutral	None	None	None	None	N
S/Q	0.4094	ambiguous	0.3895	ambiguous	-0.577	Destabilizing	0.567	D	0.671	neutral	None	None	None	None	N
S/R	0.5587	ambiguous	0.5294	ambiguous	-0.576	Destabilizing	0.497	N	0.687	prob.neutral	N	0.47437016	None	None	N
S/T	0.0613	likely_benign	0.0682	benign	-0.489	Destabilizing	0.004	N	0.438	neutral	N	0.423573194	None	None	N
S/V	0.108	likely_benign	0.113	benign	-0.102	Destabilizing	0.396	N	0.712	prob.delet.	None	None	None	None	N
S/W	0.2285	likely_benign	0.224	benign	-0.927	Destabilizing	0.968	D	0.764	deleterious	None	None	None	None	N
S/Y	0.1077	likely_benign	0.1079	benign	-0.449	Destabilizing	0.89	D	0.753	deleterious	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.