TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33746	101461;101462;101463	chr2:178535379;178535378;178535377	chr2:179400106;179400105;179400104
N2AB	32105	96538;96539;96540	chr2:178535379;178535378;178535377	chr2:179400106;179400105;179400104
N2A	31178	93757;93758;93759	chr2:178535379;178535378;178535377	chr2:179400106;179400105;179400104
N2B	24681	74266;74267;74268	chr2:178535379;178535378;178535377	chr2:179400106;179400105;179400104
Novex-1	24806	74641;74642;74643	chr2:178535379;178535378;178535377	chr2:179400106;179400105;179400104
Novex-2	24873	74842;74843;74844	chr2:178535379;178535378;178535377	chr2:179400106;179400105;179400104
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Fn3-132
• Domain position: 58
• Structural Position: 90
• Q(SASA): 0.4485
• 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
R/C	rs199594729	-0.478	1.0	N	0.532	0.358	0.667503297862	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	1.77E-05	0
R/C	rs199594729	-0.478	1.0	N	0.532	0.358	0.667503297862	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	0	1.96412E-04	0	0	0	None	0	0	2.94E-05	0	0
R/C	rs199594729	-0.478	1.0	N	0.532	0.358	0.667503297862	gnomAD-4.0.0	9.91489E-06	None	None	None	None	N	None	2.67008E-05	5.00033E-05	None	0	4.45494E-05	None	0	0	4.23786E-06	1.09786E-05	4.80261E-05
R/H	rs372584865	-1.193	0.067	N	0.345	0.203	None	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	3.27E-05	None	0	1.77E-05	0
R/H	rs372584865	-1.193	0.067	N	0.345	0.203	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/H	rs372584865	-1.193	0.067	N	0.345	0.203	None	gnomAD-4.0.0	1.61112E-05	None	None	None	None	N	None	1.33522E-05	1.66672E-05	None	0	0	None	0	0	1.69512E-05	2.19553E-05	3.20184E-05
R/P	rs372584865	None	0.994	N	0.555	0.331	0.50466331119	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/P	rs372584865	None	0.994	N	0.555	0.331	0.50466331119	gnomAD-4.0.0	2.47865E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.39024E-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
R/A	0.4217	ambiguous	0.3856	ambiguous	-0.274	Destabilizing	0.729	D	0.43	neutral	None	None	None	None	N
R/C	0.186	likely_benign	0.1691	benign	-0.361	Destabilizing	1.0	D	0.532	neutral	N	0.518540304	None	None	N
R/D	0.705	likely_pathogenic	0.6813	pathogenic	0.037	Stabilizing	0.929	D	0.525	neutral	None	None	None	None	N
R/E	0.4004	ambiguous	0.3786	ambiguous	0.147	Stabilizing	0.617	D	0.471	neutral	None	None	None	None	N
R/F	0.6689	likely_pathogenic	0.6409	pathogenic	-0.25	Destabilizing	0.974	D	0.547	neutral	None	None	None	None	N
R/G	0.3258	likely_benign	0.2958	benign	-0.542	Destabilizing	0.911	D	0.47	neutral	N	0.513902488	None	None	N
R/H	0.1017	likely_benign	0.0844	benign	-0.997	Destabilizing	0.067	N	0.345	neutral	N	0.442330392	None	None	N
R/I	0.3907	ambiguous	0.4102	ambiguous	0.42	Stabilizing	0.975	D	0.549	neutral	None	None	None	None	N
R/K	0.1173	likely_benign	0.1065	benign	-0.283	Destabilizing	0.39	N	0.491	neutral	None	None	None	None	N
R/L	0.3652	ambiguous	0.3464	ambiguous	0.42	Stabilizing	0.954	D	0.529	neutral	N	0.514249205	None	None	N
R/M	0.4126	ambiguous	0.4129	ambiguous	-0.093	Destabilizing	0.992	D	0.577	neutral	None	None	None	None	N
R/N	0.5002	ambiguous	0.4711	ambiguous	-0.007	Destabilizing	0.929	D	0.468	neutral	None	None	None	None	N
R/P	0.9482	likely_pathogenic	0.9584	pathogenic	0.211	Stabilizing	0.994	D	0.555	neutral	N	0.521887253	None	None	N
R/Q	0.1088	likely_benign	0.0978	benign	-0.081	Destabilizing	0.951	D	0.526	neutral	None	None	None	None	N
R/S	0.3911	ambiguous	0.3545	ambiguous	-0.525	Destabilizing	0.29	N	0.312	neutral	N	0.402710424	None	None	N
R/T	0.2222	likely_benign	0.2184	benign	-0.247	Destabilizing	0.867	D	0.469	neutral	None	None	None	None	N
R/V	0.4216	ambiguous	0.4225	ambiguous	0.211	Stabilizing	0.888	D	0.559	neutral	None	None	None	None	N
R/W	0.3375	likely_benign	0.3073	benign	-0.136	Destabilizing	0.999	D	0.551	neutral	None	None	None	None	N
R/Y	0.5197	ambiguous	0.4687	ambiguous	0.22	Stabilizing	0.948	D	0.555	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.