TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17565	52918;52919;52920	chr2:178608190;178608189;178608188	chr2:179472917;179472916;179472915
N2AB	15924	47995;47996;47997	chr2:178608190;178608189;178608188	chr2:179472917;179472916;179472915
N2A	14997	45214;45215;45216	chr2:178608190;178608189;178608188	chr2:179472917;179472916;179472915
N2B	8500	25723;25724;25725	chr2:178608190;178608189;178608188	chr2:179472917;179472916;179472915
Novex-1	8625	26098;26099;26100	chr2:178608190;178608189;178608188	chr2:179472917;179472916;179472915
Novex-2	8692	26299;26300;26301	chr2:178608190;178608189;178608188	chr2:179472917;179472916;179472915
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-15
• Domain position: 96
• Structural Position: 131
• Q(SASA): 0.6281
• 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
H/D	rs370126872	0.238	0.001	N	0.245	0.082	0.141422826196	gnomAD-2.1.1	2.94E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.46E-05	0
H/D	rs370126872	0.238	0.001	N	0.245	0.082	0.141422826196	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	5.89E-05	0	0
H/D	rs370126872	0.238	0.001	N	0.245	0.082	0.141422826196	gnomAD-4.0.0	3.43237E-05	None	None	None	None	N	None	1.34416E-05	0	None	0	0	None	1.57684E-05	4.98836E-04	4.25862E-05	0	0
H/N	None	0.204	0.001	N	0.12	0.067	None	gnomAD-2.1.1	1.85E-05	None	None	None	None	N	None	0	5.92E-05	None	0	0	None	0	None	0	2.42E-05	0
H/N	None	0.204	0.001	N	0.12	0.067	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
H/N	None	0.204	0.001	N	0.12	0.067	None	gnomAD-4.0.0	4.99254E-06	None	None	None	None	N	None	0	5.1212E-05	None	0	0	None	0	0	4.25861E-06	0	0
H/Q	None	None	None	N	0.069	0.089	0.0920862733494	gnomAD-4.0.0	1.61956E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.90402E-06	0	0
H/R	None	None	None	N	0.056	0.147	0.0482279557977	gnomAD-4.0.0	1.62009E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.07977E-05
H/Y	rs370126872	0.671	0.006	N	0.173	0.101	0.180583059064	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	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
H/A	0.1746	likely_benign	0.1767	benign	-0.107	Destabilizing	None	N	0.248	neutral	None	None	None	None	N
H/C	0.0965	likely_benign	0.091	benign	0.489	Stabilizing	0.176	N	0.41	neutral	None	None	None	None	N
H/D	0.2587	likely_benign	0.2641	benign	0.037	Stabilizing	0.001	N	0.245	neutral	N	0.408441531	None	None	N
H/E	0.1803	likely_benign	0.1787	benign	0.052	Stabilizing	None	N	0.087	neutral	None	None	None	None	N
H/F	0.2433	likely_benign	0.231	benign	0.197	Stabilizing	0.02	N	0.427	neutral	None	None	None	None	N
H/G	0.2208	likely_benign	0.2337	benign	-0.38	Destabilizing	None	N	0.278	neutral	None	None	None	None	N
H/I	0.2052	likely_benign	0.1954	benign	0.585	Stabilizing	0.008	N	0.419	neutral	None	None	None	None	N
H/K	0.1195	likely_benign	0.1235	benign	-0.07	Destabilizing	None	N	0.248	neutral	None	None	None	None	N
H/L	0.0775	likely_benign	0.0853	benign	0.585	Stabilizing	0.001	N	0.285	neutral	N	0.371694083	None	None	N
H/M	0.2578	likely_benign	0.2563	benign	0.579	Stabilizing	0.02	N	0.5	neutral	None	None	None	None	N
H/N	0.1126	likely_benign	0.1144	benign	0.158	Stabilizing	0.001	N	0.12	neutral	N	0.422872265	None	None	N
H/P	0.6397	likely_pathogenic	0.6719	pathogenic	0.379	Stabilizing	0.006	N	0.268	neutral	N	0.369133781	None	None	N
H/Q	0.0833	likely_benign	0.079	benign	0.203	Stabilizing	None	N	0.069	neutral	N	0.308066679	None	None	N
H/R	0.0612	likely_benign	0.0597	benign	-0.401	Destabilizing	None	N	0.056	neutral	N	0.324478927	None	None	N
H/S	0.1607	likely_benign	0.1639	benign	0.101	Stabilizing	None	N	0.102	neutral	None	None	None	None	N
H/T	0.168	likely_benign	0.1685	benign	0.205	Stabilizing	0.001	N	0.275	neutral	None	None	None	None	N
H/V	0.1464	likely_benign	0.1482	benign	0.379	Stabilizing	0.002	N	0.347	neutral	None	None	None	None	N
H/W	0.2877	likely_benign	0.2809	benign	0.193	Stabilizing	0.176	N	0.395	neutral	None	None	None	None	N
H/Y	0.0975	likely_benign	0.0927	benign	0.607	Stabilizing	0.006	N	0.173	neutral	N	0.423565699	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.