Submissions for variant NM_001927.4(DES):c.736G>A (p.Glu246Lys)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues	RCV003315214	SCV004014840	likely pathogenic	Dilated cardiomyopathy 1I	2023-07-04	criteria provided, single submitter	clinical testing
Invitae	RCV003777288	SCV004573276	uncertain significance	Desmin-related myofibrillar myopathy	2023-12-02	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 246 of the DES protein (p.Glu246Lys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DES-related conditions. ClinVar contains an entry for this variant (Variation ID: 2573100). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.