TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15437	46534;46535;46536	chr2:178620108;178620107;178620106	chr2:179484835;179484834;179484833
N2AB	13796	41611;41612;41613	chr2:178620108;178620107;178620106	chr2:179484835;179484834;179484833
N2A	12869	38830;38831;38832	chr2:178620108;178620107;178620106	chr2:179484835;179484834;179484833
N2B	6372	19339;19340;19341	chr2:178620108;178620107;178620106	chr2:179484835;179484834;179484833
Novex-1	6497	19714;19715;19716	chr2:178620108;178620107;178620106	chr2:179484835;179484834;179484833
Novex-2	6564	19915;19916;19917	chr2:178620108;178620107;178620106	chr2:179484835;179484834;179484833
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-106
• Domain position: 47
• Structural Position: 122
• Q(SASA): 0.3532
• 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
K/T	rs552087956	-1.017	0.001	N	0.152	0.186	0.227260227426	gnomAD-2.1.1	4.1E-06	None	None	None	None	N	None	6.5E-05	0	None	0	0	None	0	None	0	0	0
K/T	rs552087956	-1.017	0.001	N	0.152	0.186	0.227260227426	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
K/T	rs552087956	-1.017	0.001	N	0.152	0.186	0.227260227426	1000 genomes	1.99681E-04	None	None	None	None	N	None	8E-04	0	None	None	0	0	None	None	None	0	None
K/T	rs552087956	-1.017	0.001	N	0.152	0.186	0.227260227426	gnomAD-4.0.0	6.57895E-06	None	None	None	None	N	None	2.40801E-05	0	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
K/A	0.3364	likely_benign	0.3019	benign	-0.732	Destabilizing	None	N	0.155	neutral	None	None	None	None	N
K/C	0.6085	likely_pathogenic	0.5947	pathogenic	-0.809	Destabilizing	0.883	D	0.399	neutral	None	None	None	None	N
K/D	0.6538	likely_pathogenic	0.6116	pathogenic	-0.056	Destabilizing	0.22	N	0.324	neutral	None	None	None	None	N
K/E	0.2487	likely_benign	0.1996	benign	0.107	Stabilizing	0.042	N	0.259	neutral	N	0.467748443	None	None	N
K/F	0.7216	likely_pathogenic	0.6811	pathogenic	-0.231	Destabilizing	0.497	N	0.431	neutral	None	None	None	None	N
K/G	0.5563	ambiguous	0.5359	ambiguous	-1.133	Destabilizing	0.124	N	0.383	neutral	None	None	None	None	N
K/H	0.2226	likely_benign	0.1897	benign	-1.211	Destabilizing	0.667	D	0.387	neutral	None	None	None	None	N
K/I	0.2482	likely_benign	0.2127	benign	0.327	Stabilizing	0.001	N	0.303	neutral	N	0.500615051	None	None	N
K/L	0.2926	likely_benign	0.2678	benign	0.327	Stabilizing	0.02	N	0.329	neutral	None	None	None	None	N
K/M	0.2709	likely_benign	0.2161	benign	0.009	Stabilizing	0.497	N	0.389	neutral	None	None	None	None	N
K/N	0.4109	ambiguous	0.3817	ambiguous	-0.66	Destabilizing	0.175	N	0.275	neutral	N	0.510349703	None	None	N
K/P	0.9516	likely_pathogenic	0.9586	pathogenic	0.003	Stabilizing	0.364	N	0.397	neutral	None	None	None	None	N
K/Q	0.1164	likely_benign	0.0992	benign	-0.606	Destabilizing	0.003	N	0.111	neutral	N	0.440517793	None	None	N
K/R	0.0927	likely_benign	0.0774	benign	-0.552	Destabilizing	0.096	N	0.237	neutral	N	0.501573347	None	None	N
K/S	0.3698	ambiguous	0.3354	benign	-1.37	Destabilizing	0.055	N	0.261	neutral	None	None	None	None	N
K/T	0.1396	likely_benign	0.1118	benign	-0.977	Destabilizing	0.001	N	0.152	neutral	N	0.488550706	None	None	N
K/V	0.2515	likely_benign	0.2122	benign	0.003	Stabilizing	0.02	N	0.347	neutral	None	None	None	None	N
K/W	0.7649	likely_pathogenic	0.7247	pathogenic	-0.097	Destabilizing	0.958	D	0.429	neutral	None	None	None	None	N
K/Y	0.6014	likely_pathogenic	0.5551	ambiguous	0.178	Stabilizing	0.667	D	0.407	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.