TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14693	44302;44303;44304	chr2:178630881;178630880;178630879	chr2:179495608;179495607;179495606
N2AB	13052	39379;39380;39381	chr2:178630881;178630880;178630879	chr2:179495608;179495607;179495606
N2A	12125	36598;36599;36600	chr2:178630881;178630880;178630879	chr2:179495608;179495607;179495606
N2B	5628	17107;17108;17109	chr2:178630881;178630880;178630879	chr2:179495608;179495607;179495606
Novex-1	5753	17482;17483;17484	chr2:178630881;178630880;178630879	chr2:179495608;179495607;179495606
Novex-2	5820	17683;17684;17685	chr2:178630881;178630880;178630879	chr2:179495608;179495607;179495606
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGC
• RefSeq wild type template codon: GCG
• Domain: Ig-98
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.7588
• 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	rs200445568	-0.114	1.0	N	0.613	0.369	None	gnomAD-2.1.1	2.32251E-04	None	None	None	None	N	None	2.35693E-03	1.41483E-04	None	0	0	None	3.27E-05	None	0	1.56E-05	0
R/C	rs200445568	-0.114	1.0	N	0.613	0.369	None	gnomAD-3.1.2	7.56479E-04	None	None	None	None	N	None	2.51123E-03	4.59559E-04	0	0	0	None	0	0	1.47E-05	0	1.43678E-03
R/C	rs200445568	-0.114	1.0	N	0.613	0.369	None	1000 genomes	5.99042E-04	None	None	None	None	N	None	2.3E-03	0	None	None	0	0	None	None	None	0	None
R/C	rs200445568	-0.114	1.0	N	0.613	0.369	None	gnomAD-4.0.0	1.50009E-04	None	None	None	None	N	None	2.50733E-03	2.33505E-04	None	0	0	None	0	1.65235E-04	1.27171E-05	4.393E-05	3.20277E-04
R/H	rs746380621	-0.659	1.0	N	0.644	0.291	0.146414634003	gnomAD-2.1.1	6.79E-05	None	None	None	None	N	None	0	2.83E-05	None	9.67E-05	6.71141E-04	None	6.54E-05	None	0	7.81E-06	1.40568E-04
R/H	rs746380621	-0.659	1.0	N	0.644	0.291	0.146414634003	gnomAD-3.1.2	5.26E-05	None	None	None	None	N	None	2.41E-05	0	0	2.88517E-04	3.87747E-04	None	0	0	4.41E-05	2.06954E-04	0
R/H	rs746380621	-0.659	1.0	N	0.644	0.291	0.146414634003	gnomAD-4.0.0	4.71128E-05	None	None	None	None	N	None	2.67058E-05	5.0045E-05	None	4.05625E-04	4.69211E-04	None	0	0	1.69563E-05	1.31775E-04	9.612E-05

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	0.3385	likely_benign	0.3121	benign	-0.141	Destabilizing	0.926	D	0.605	neutral	None	None	None	None	N
R/C	0.1	likely_benign	0.0992	benign	-0.271	Destabilizing	1.0	D	0.613	neutral	N	0.43742205	None	None	N
R/D	0.5814	likely_pathogenic	0.5161	ambiguous	-0.037	Destabilizing	0.995	D	0.614	neutral	None	None	None	None	N
R/E	0.3291	likely_benign	0.3194	benign	0.064	Stabilizing	0.968	D	0.631	neutral	None	None	None	None	N
R/F	0.279	likely_benign	0.2961	benign	-0.178	Destabilizing	0.998	D	0.632	neutral	None	None	None	None	N
R/G	0.3119	likely_benign	0.249	benign	-0.394	Destabilizing	0.992	D	0.611	neutral	N	0.455962868	None	None	N
R/H	0.0576	likely_benign	0.0617	benign	-0.875	Destabilizing	1.0	D	0.644	neutral	N	0.45518166	None	None	N
R/I	0.1442	likely_benign	0.1597	benign	0.508	Stabilizing	0.991	D	0.653	prob.neutral	None	None	None	None	N
R/K	0.1122	likely_benign	0.1319	benign	-0.195	Destabilizing	0.29	N	0.379	neutral	None	None	None	None	N
R/L	0.1573	likely_benign	0.1482	benign	0.508	Stabilizing	0.983	D	0.603	neutral	N	0.413831451	None	None	N
R/M	0.2557	likely_benign	0.2765	benign	-0.008	Destabilizing	1.0	D	0.613	neutral	None	None	None	None	N
R/N	0.3787	ambiguous	0.3521	ambiguous	0.043	Stabilizing	0.984	D	0.639	neutral	None	None	None	None	N
R/P	0.9012	likely_pathogenic	0.8227	pathogenic	0.313	Stabilizing	0.999	D	0.665	prob.neutral	N	0.497001032	None	None	N
R/Q	0.0984	likely_benign	0.1001	benign	-0.024	Destabilizing	0.991	D	0.664	prob.neutral	None	None	None	None	N
R/S	0.314	likely_benign	0.2934	benign	-0.401	Destabilizing	0.967	D	0.593	neutral	N	0.433877692	None	None	N
R/T	0.153	likely_benign	0.1662	benign	-0.139	Destabilizing	0.29	N	0.479	neutral	None	None	None	None	N
R/V	0.1904	likely_benign	0.2214	benign	0.313	Stabilizing	0.991	D	0.601	neutral	None	None	None	None	N
R/W	0.1227	likely_benign	0.1188	benign	-0.126	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	N
R/Y	0.1928	likely_benign	0.1926	benign	0.253	Stabilizing	0.998	D	0.649	prob.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.