TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18162	54709;54710;54711	chr2:178604203;178604202;178604201	chr2:179468930;179468929;179468928
N2AB	16521	49786;49787;49788	chr2:178604203;178604202;178604201	chr2:179468930;179468929;179468928
N2A	15594	47005;47006;47007	chr2:178604203;178604202;178604201	chr2:179468930;179468929;179468928
N2B	9097	27514;27515;27516	chr2:178604203;178604202;178604201	chr2:179468930;179468929;179468928
Novex-1	9222	27889;27890;27891	chr2:178604203;178604202;178604201	chr2:179468930;179468929;179468928
Novex-2	9289	28090;28091;28092	chr2:178604203;178604202;178604201	chr2:179468930;179468929;179468928
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-19
• Domain position: 98
• Structural Position: 132
• Q(SASA): 0.615
• 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
D/V	None	None	1.0	N	0.709	0.531	0.641425284928	gnomAD-4.0.0	1.59632E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43843E-05	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
D/A	0.7479	likely_pathogenic	0.6358	pathogenic	-0.113	Destabilizing	1.0	D	0.663	prob.neutral	N	0.515705069	None	None	N
D/C	0.9584	likely_pathogenic	0.9177	pathogenic	-0.063	Destabilizing	1.0	D	0.738	deleterious	None	None	None	None	N
D/E	0.6673	likely_pathogenic	0.5776	pathogenic	-0.274	Destabilizing	0.999	D	0.496	neutral	N	0.495041795	None	None	N
D/F	0.9301	likely_pathogenic	0.8511	pathogenic	-0.143	Destabilizing	1.0	D	0.738	deleterious	None	None	None	None	N
D/G	0.7771	likely_pathogenic	0.6768	pathogenic	-0.277	Destabilizing	1.0	D	0.732	deleterious	N	0.47155246	None	None	N
D/H	0.8096	likely_pathogenic	0.6527	pathogenic	0.196	Stabilizing	1.0	D	0.777	deleterious	N	0.505181431	None	None	N
D/I	0.9156	likely_pathogenic	0.8423	pathogenic	0.259	Stabilizing	1.0	D	0.734	deleterious	None	None	None	None	N
D/K	0.9397	likely_pathogenic	0.9094	pathogenic	0.297	Stabilizing	1.0	D	0.723	deleterious	None	None	None	None	N
D/L	0.8707	likely_pathogenic	0.7717	pathogenic	0.259	Stabilizing	1.0	D	0.729	deleterious	None	None	None	None	N
D/M	0.9596	likely_pathogenic	0.9228	pathogenic	0.19	Stabilizing	1.0	D	0.693	prob.delet.	None	None	None	None	N
D/N	0.2871	likely_benign	0.2508	benign	0.093	Stabilizing	1.0	D	0.676	prob.neutral	N	0.489193258	None	None	N
D/P	0.9013	likely_pathogenic	0.8787	pathogenic	0.156	Stabilizing	1.0	D	0.721	deleterious	None	None	None	None	N
D/Q	0.9169	likely_pathogenic	0.8687	pathogenic	0.105	Stabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
D/R	0.9551	likely_pathogenic	0.9295	pathogenic	0.516	Stabilizing	1.0	D	0.722	deleterious	None	None	None	None	N
D/S	0.5576	ambiguous	0.4529	ambiguous	-0.026	Destabilizing	1.0	D	0.723	deleterious	None	None	None	None	N
D/T	0.8297	likely_pathogenic	0.7499	pathogenic	0.096	Stabilizing	1.0	D	0.723	deleterious	None	None	None	None	N
D/V	0.8117	likely_pathogenic	0.6995	pathogenic	0.156	Stabilizing	1.0	D	0.709	prob.delet.	N	0.478678803	None	None	N
D/W	0.9849	likely_pathogenic	0.9707	pathogenic	-0.072	Destabilizing	1.0	D	0.687	prob.delet.	None	None	None	None	N
D/Y	0.5992	likely_pathogenic	0.4235	ambiguous	0.078	Stabilizing	1.0	D	0.735	deleterious	N	0.506797584	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.