ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.145A>G (p.Thr49Ala) (rs142059019)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000037992 SCV000061658 likely benign not specified 2015-05-18 criteria provided, single submitter clinical testing p.Thr49Ala in exon 1 of DSP: This variant is not expected to have clinical signi ficance due to a lack of conservation across species, including mammals. Of note , 3 mammals (lesser Egyptian jerboa, white rhinoceros and hedgehog shrew) have a n alanine (Ala) at this position despite moderate nearby amino acid conservation . In addition, computational prediction tools do not suggest a high likelihood o f impact to the protein.
GeneDx RCV000766870 SCV000233656 uncertain significance not provided 2014-03-22 criteria provided, single submitter clinical testing p.Thr49Ala (ACC>GCC): c.145 A>G in exon 1 of the DSP gene (NM_004415.2). The T49A variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The T49A variant was not observed at a significant frequency in approximately 6400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The T49A variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across species. Additionally, in silico analysis predicts this variant likely does not alter the protein structure/function. No other missense mutations in nearby residues have been reported in association with ARVC.Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in ARVC panel(s).

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