TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9113	27562;27563;27564	chr2:178712585;178712584;178712583	chr2:179577312;179577311;179577310
N2AB	8796	26611;26612;26613	chr2:178712585;178712584;178712583	chr2:179577312;179577311;179577310
N2A	7869	23830;23831;23832	chr2:178712585;178712584;178712583	chr2:179577312;179577311;179577310
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-77
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.3701
• 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/I	rs775352248	0.378	None	N	0.259	0.23	0.510758216515	gnomAD-2.1.1	8.11E-06	None	None	None	None	N	None	0	0	None	0	1.12423E-04	None	0	None	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	0.1658	likely_benign	0.1801	benign	-0.352	Destabilizing	None	N	0.101	neutral	None	None	None	None	N
K/C	0.4835	ambiguous	0.4708	ambiguous	-0.447	Destabilizing	0.935	D	0.303	neutral	None	None	None	None	N
K/D	0.4186	ambiguous	0.453	ambiguous	0.258	Stabilizing	0.149	N	0.331	neutral	None	None	None	None	N
K/E	0.1042	likely_benign	0.1126	benign	0.323	Stabilizing	0.062	N	0.173	neutral	N	0.496733385	None	None	N
K/F	0.4819	ambiguous	0.5046	ambiguous	-0.305	Destabilizing	0.38	N	0.333	neutral	None	None	None	None	N
K/G	0.3162	likely_benign	0.3126	benign	-0.641	Destabilizing	0.081	N	0.274	neutral	None	None	None	None	N
K/H	0.1792	likely_benign	0.1843	benign	-0.93	Destabilizing	0.555	D	0.252	neutral	None	None	None	None	N
K/I	0.1493	likely_benign	0.1775	benign	0.359	Stabilizing	None	N	0.259	neutral	N	0.506941044	None	None	N
K/L	0.192	likely_benign	0.1995	benign	0.359	Stabilizing	0.012	N	0.232	neutral	None	None	None	None	N
K/M	0.1334	likely_benign	0.1477	benign	0.18	Stabilizing	0.38	N	0.251	neutral	None	None	None	None	N
K/N	0.2259	likely_benign	0.2502	benign	-0.053	Destabilizing	0.117	N	0.26	neutral	N	0.494659686	None	None	N
K/P	0.8689	likely_pathogenic	0.8517	pathogenic	0.153	Stabilizing	0.555	D	0.313	neutral	None	None	None	None	N
K/Q	0.0871	likely_benign	0.0889	benign	-0.176	Destabilizing	0.117	N	0.269	neutral	D	0.525978856	None	None	N
K/R	0.0705	likely_benign	0.068	benign	-0.24	Destabilizing	None	N	0.074	neutral	N	0.48297744	None	None	N
K/S	0.1987	likely_benign	0.2186	benign	-0.711	Destabilizing	0.035	N	0.157	neutral	None	None	None	None	N
K/T	0.0808	likely_benign	0.0918	benign	-0.456	Destabilizing	0.117	N	0.281	neutral	N	0.482689439	None	None	N
K/V	0.1341	likely_benign	0.1521	benign	0.153	Stabilizing	0.012	N	0.25	neutral	None	None	None	None	N
K/W	0.619	likely_pathogenic	0.6219	pathogenic	-0.202	Destabilizing	0.935	D	0.399	neutral	None	None	None	None	N
K/Y	0.3967	ambiguous	0.411	ambiguous	0.116	Stabilizing	0.555	D	0.299	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.