Submissions for variant NM_003289.4(TPM2):c.349G>A (p.Glu117Lys)

dbSNP: rs104894129

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000128681	SCV000332318	pathogenic	not provided	2017-05-17	criteria provided, single submitter	clinical testing
GeneDx	RCV000128681	SCV000521269	pathogenic	not provided	2021-07-14	criteria provided, single submitter	clinical testing	Published functional studies demonstrate a damaging effect showing the variant to significantly inhibit formation of strong binding actomyosin disruptive to the ATPase cycle, impaired activation of contractility, and reduction in thin filament activation (Marttila et al., 2012; Karpicheva et al., 2013; Karpicheva et al., 2014); Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24692096, 22084935, 11738357, 31321302, 24077912, 27535533, 23689010, 24657080)
Invitae	RCV000531827	SCV000630167	pathogenic	Arthrogryposis, distal, type 1A	2022-03-18	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 12462). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects TPM2 function (PMID: 22084935, 23689010, 23886664, 24657080). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This missense change has been observed in individual(s) with congenital fiber type disproportion (CFTD), distal arthrogryposis (DA) and nemaline myopathy (NM) (PMID: 11738357, 24692096). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 117 of the TPM2 protein (p.Glu117Lys).
OMIM	RCV000013278	SCV000033525	pathogenic	Congenital myopathy 23	2002-02-01	no assertion criteria provided	literature only
GeneReviews	RCV000013278	SCV000058547	not provided	Congenital myopathy 23		no assertion provided	literature only
TPM2 homepage - Leiden Muscular Dystrophy pages	RCV000128681	SCV000172321	not provided	not provided		no assertion provided	not provided